CN112029860B - Marker molecule related to colorectal cancer prognosis and detection kit - Google Patents
Marker molecule related to colorectal cancer prognosis and detection kit Download PDFInfo
- Publication number
- CN112029860B CN112029860B CN202010915926.9A CN202010915926A CN112029860B CN 112029860 B CN112029860 B CN 112029860B CN 202010915926 A CN202010915926 A CN 202010915926A CN 112029860 B CN112029860 B CN 112029860B
- Authority
- CN
- China
- Prior art keywords
- seq
- prognosis
- rectal cancer
- marker molecule
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B25/10—Gene or protein expression profiling; Expression-ratio estimation or normalisation
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Theoretical Computer Science (AREA)
- Bioinformatics & Computational Biology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Evolutionary Biology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Computer Vision & Pattern Recognition (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Artificial Intelligence (AREA)
- Bioethics (AREA)
- Oncology (AREA)
- Data Mining & Analysis (AREA)
- Databases & Information Systems (AREA)
- Epidemiology (AREA)
- Evolutionary Computation (AREA)
- Public Health (AREA)
- Software Systems (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention relates to a marker molecule related to colorectal cancer prognosis, which comprises at least one gene sequence shown as SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10. The marker molecules provided by the invention are a gene set modified by 6-methyladenine, are verified to be highly related to the prognosis of rectal cancer, and can be used as a biomarker for the prognosis evaluation of clinical rectal cancer patients, so that the life quality of the patients is improved.
Description
Technical Field
The invention relates to the field of cancer treatment and prognosis evaluation, in particular to a marker molecule and a detection kit related to colorectal cancer prognosis.
Background
Rectal cancer is the third most prevalent cancer occurring worldwide, with mortality rates ranked second among cancers. 30% of the sites of rectal cancer development are located between the dentate line to the rectosigmoid junction, one of the most common malignancies of the digestive tract. Rectal cancer is low in location and is easily diagnosed by digital rectal examination and sigmoidoscopy. But the position of the pelvic cavity is deep, so the anatomical relationship is complex, the operation is not easy to be thorough, and the postoperative recurrence rate is high. In addition, the colon cancer is easy to transfer due to the rapid occurrence of the colon cancer, so that the survival prognosis of colon cancer patients is generally poor. With the innovation of bioinformatics technology and medical treatment, in order to more accurately detect individual prognosis and implement appropriate adjuvant therapy, methods such as high-throughput sequencing and bioinformatics analysis can be utilized to search for rectal cancer occurrence, diagnosis and prognosis indexes on a molecular level to improve the quality of life of patients. Genomic epigenetic modifications, such as histone modifications, RNA modifications, and DNA methylation, play a key role in the development of tumors.
6-Methyl adenine (m) 6 A) The modification is one of the most common post-transcriptional modifications of eukaryotic mRNA, and is involved in biological processes such as DNA damage repair and RNA metabolism, such as degradation of mRNA, shear processing, transport, translation, lncRNA, and microRNA synthesis. m is 6 The A modification is mainly composed of m 6 A regulators mediate the addition, elimination and recognition of methylation, including "writers", "readers" and "erasers", respectively. Currently known "writers" include METTL3, METTL14, METTL16, WTAP, RBM15/15B and KIAA1429; "erasers" includes FTO and ALKBH5; "readers" includes YTHDF1-3, HNRNP family, IGF2BP family, etc. The study of 6-methyladenine modification in tumors is receiving increasing attention, but the relation between 6-methyladenine modification and rectal cancer is poorly understood in the art.
Disclosure of Invention
The first object of the present invention is to provide an isolated marker molecule associated with prognosis of rectal cancer, comprising: at least one gene sequence shown in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10.
Specifically, the marker molecule related to the colorectal cancer prognosis provided by the invention can be any one sequence of SEQ ID NO. 1-10, and can also comprise any two, three, four, five, six, seven, eight, nine or all ten sequences.
Among them, the gene sequence shown in SEQ ID NO:1 (also known as ADAMTSL 1) is a component of extracellular matrix, and may play a role in cell or cell-matrix interactions, or may modulate other ADAMTS proteases. ADAMTSL1 is highly expressed in skeletal muscle, while it appears hypermethylated in ER-positive breast cancer cells. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence shown in SEQ ID NO:2 (also known as CSMD 2) may influence the development and differentiation of central nervous system lymphoma (PCNSL). At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence (also known as FAM 13C) shown in SEQ ID NO. 3 is an independent prognostic marker for prostate cancer. High expression of FAM13C was significantly associated with late pT, high Gleason, lymph node positive, early biochemical recurrence. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence shown in SEQ ID NO. 4 (also known as FAM 184A) may be involved in the development of cancer, particularly in the prognosis of patients with endometrial cancer. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence (also known as KLHL 4) shown as SEQ ID NO:5 can be used as a target gene of IGFBP5 and jointly participate in the anti-estrogen desensitization treatment process of ER positive breast cancer cells through a PI3K/Akt signal pathway. At present, no report that the gene sequence is related to the prognosis of the rectal cancer is found.
The gene sequence (also named OLFML 2B) shown in SEQ ID NO. 6 may play a carcinogenic role in the occurrence and development of gastric cancer, and the over-expression of OLFML2B in gastric cancer may become a new gastric cancer diagnosis and prognosis target. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence shown in SEQ ID NO. 7 (also known as PDZD 4) is expressed in fetal and adult brain tissues and may play a role in cell growth. PDZD4 is likely involved in brain function and development and is significantly increased in synovial sarcoma cells and thus associated with tumor cell proliferation. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence shown in SEQ ID NO. 8 (also known as SEC14L 5) is a gene of the SEC14 protein family. SEC14L5 is significantly associated with the development of post-traumatic stress syndrome, and may also be a risk gene for the development of intracranial aneurysms. At present, reports that the gene sequence is related to the prognosis of the rectal cancer are not found.
The gene sequence (also named SETBP 1) shown as SEQ ID NO. 9 can be used as a target gene of miR-211-5p in triple negative breast cancer, and can interact with miR-211-5p to inhibit proliferation, invasion, migration and transfer capacity of breast cancer cells. At present, no report that the gene sequence is related to the prognosis of the rectal cancer is found.
The gene sequence shown in SEQ ID NO:10 (also known as TMEM 132B) may be involved in the development of intracranial aneurysms. At present, no report that the gene sequence is related to the prognosis of the rectal cancer is found.
The marker molecules provided by the invention are a gene set modified by 6-methyladenine, are verified to be highly related to the prognosis of rectal cancer, and can be used as a biomarker for the prognosis evaluation of clinical rectal cancer patients, so that the life quality of the patients is improved.
The second object of the present invention is to provide a test kit for evaluating the prognostic effect of rectal cancer, which comprises: reagents for detecting marker molecules associated with the prognosis of rectal cancer; the marker molecule comprises: at least one gene sequence shown in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10.
Specifically, the marker molecule can be any one of SEQ ID NO. 1-10, and can also comprise any two, three, four, five, six, seven, eight, nine or all ten of the sequences.
As a preferred embodiment of the present invention, the reagent for detecting a marker molecule comprises a primer pair for the marker molecule for detecting the expression level of the marker molecule in a patient sample.
As a preferable scheme of the invention, the reagent for detecting the marker molecules comprises specific fluorescent probes aiming at the marker molecules, and the marker molecules in the sample of the patient are quantitatively detected by monitoring fluorescent signals in a PCR system in real time.
It is a third object of the present invention to provide an evaluation system for the prognostic effect of rectal cancer, comprising: (1) The data input module is used for inputting the content detection result of the marker molecules related to the prognosis of the rectal cancer into the model calculation module; (2) The model calculation module is used for calculating and processing the input content detection result to obtain the prognosis effect data of the detected patient; (3) And the result output module is used for evaluating the prognosis effect data of the detected patient according to the evaluation standard of the prognosis effect of the rectal cancer and outputting an evaluation result.
The marker molecules relevant to the prognosis of the rectal cancer comprise: at least one gene sequence shown in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10.
Specifically, the marker molecule can be any one of SEQ ID NO. 1-10, and can also comprise any two, three, four, five, six, seven, eight, nine or all ten of the sequences.
It is a fourth object of the invention to provide the use of said marker molecule, said kit or said evaluation system in the diagnosis of rectal cancer.
The fifth purpose of the invention is to provide the application of the marker molecule, the kit or the evaluation system in the prognosis evaluation of a patient with rectal cancer.
The method is based on the aspect of 6-methyladenine modification for the first time, a characteristic gene set which is modified by 6-methyladenine and is related to the prognosis of the rectal cancer is screened out from differential genes of a rectal cancer tissue and a normal tissue, and then 10 genes which are remarkably related to the prognosis of the rectal cancer are found through methods such as k-means cluster analysis, PCA analysis, COX regression analysis, ROC curve analysis, risk assessment and the like. When the risk score calculated by the characteristics is used for predicting the prognosis and clinical pathological characteristics of a tumor patient, the area value under the ROC curve is higher, which indicates that the 10 genes can well reflect the prognosis of a rectal cancer patient, and a new thought is provided for improving the diagnosis and survival prognosis of clinical rectal cancer patients.
Drawings
FIG. 1 shows rectal cancer m 6 Heat map of expression of a candidate gene over 4 min;
FIG. 2 is a k-means cluster plot of rectal cancer samples;
FIG. 3 shows rectal cancer m 6 Heat map of expression of a candidate gene among 2 subgroups;
FIG. 4 is a box plot of age between two subgroups of rectal cancer;
FIG. 5 is a WHO grading pie chart between two subgroups of rectal cancer;
FIG. 6 is a graph of survival between two sub-groups of rectal cancer;
FIG. 7 shows m 6 A protein interaction network map of candidate genes;
FIG. 8 shows m 6 A candidate gene coexpression network diagram;
FIG. 9 is a graph of principal component analysis of two subgroups (group 1, group 2);
FIG. 10 is a graph of differential gene enrichment for two subgroups (group 1, group 2);
FIG. 11 is a graph of sample survival for high and low risk groups;
FIG. 12 is a predicted effect of risk scoring for combined features on three-year survival outcomes; wherein the left graph is trailing, and the right graph is nesting;
FIG. 13 is a graph of risk score for a combination of features versus the predicted effect on subgroups; wherein the left graph is trailing, and the right graph is nesting;
FIG. 14 is a graph of the predictive effect of risk scoring for combined features on prognostic outcome; wherein the left graph is trailing, and the right graph is nesting;
FIG. 15 is a predicted effect of risk scoring on staging for a combined signature; wherein the left graph is trailing and the right graph is nesting.
Detailed Description
The following examples are intended to illustrate the invention, but are not intended to limit the scope of the invention.
Examples
1. Acquisition of data
Rectal cancer (READ) RNA-seq transcriptome data (rpkm data), rectal cancer clinical survival data (including pathology characteristics and survival time, etc.) were downloaded from TCGA, gene annotation files were downloaded from Genecode. Samples with pathological characteristics (stages of StageI, stageII, stageIII and StageIV) and RNA-seq expression data are selected to obtain 88 samples of rectal cancer.
13 widely reported m were obtained from the literature 6 A RNA methylation regulator (for m involved in different roles during methylation) 6 A RNA methylation modulators: writers (methyltransferase) -METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13; readers (binding proteins) -YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC; erasers (demethylases) -FTO, ALKBH 5). Downloading READ m from m6 avatar database 6 A related genes to obtain 1047 rectal cancers m 6 A related gene.
2. Data preprocessing and differential gene screening
1047 rectal cancers m were constructed using gene annotation files using 88 rectal cancer samples containing both pathological feature (staging StageI, stageII, stageIII, stageIV) data and RNA-seq expression data 6 Expression profiles of A-related genes (rpkm data), and rectal cancer samples were classified into four categories (StageI, stageII, stageIII, stageIV) according to their stage.
Differential expression genes were screened among four classes of samples (StageI, stagiii, stageIV) using analysis of variance. Selecting a P value adj. Pvalue corrected by Benjamini-Hochberg (FDR)<0.05 and | log2Foldchange non-woven cells>1 is used as the threshold. Among them, log2Foldchange>1, the differential gene is considered to be up-regulated, whereas log2Foldchange<-1, the differential gene is considered to be down-regulated. The larger the | log2Foldchange | is, the larger the fold difference is, and the smaller adj. 974 differentially expressed genes were selected as m 6 A candidate Gene set and use of m 6 The A candidate gene set was used to construct an expression heatmap, and the results are shown in FIG. 1.
3. Sample consistency clustering
Differential expression m in selected READ intervals 6 A related gene (i.e. 974 rectal cancers m) 6 A candidate gene) as a feature vector, and k-means clustering (k = 2) was performed on 88 samples, and the results are shown in fig. 2. Two subgroups group1 and group2 are obtained, wherein the subgroups group1 and group2 contain 47 and 41 samples, respectively. Cancer of rectum m 6 The heatmap of the expression of the A candidate gene across the 2 subgroups is shown in FIG. 3.
4. Comparative analysis of pathological features and survival time between two subgroups
Samples containing age data from both subgroups were extracted and analyzed for age differences between group1 and group2 using a T-test comparison, the results of which are shown in fig. 4. The results indicated that the difference between the ages of the two groups was not significant.
Samples containing staging data from both subgroups were extracted and analyzed for differences between the two subgroups of WHO using the chi-square test, the results are shown in figure 5. The results indicated a significant difference in WHO ranking for the two subgroups (p = 0.00337).
Samples containing survival data from both subgroups were extracted and survival analysis was performed on both subgroups using COX regression, the results are shown in fig. 6. The results show that the survival rate of the group2 subgroup is obviously improved.
5、m 6 Analysis of interaction relationships between candidate gene sets
Analysis of m Using STRING database 6 The interaction between the A candidate genes is shown in FIG. 7. The interactive network is constructed by using the Cytoscape software, and the network with more than 10 nodes is reserved, and the result is shown in figure 8. The size of the node is related to the size of the node degree, the thickness of the edge is related to the comprehensive fraction of the interaction degree between the nodes, and the color of the node is related to the differential expression multiple.
6. Screening and function analysis of differential expression genes between group1 and group2 subgroups
Constructing m of two subgroups of group1 and group2 6 The A candidate gene expression profiles were analyzed for differences in gene expression between the two subgroups using Principal Component Analysis (PCA), the results of which are shown in FIG. 9. The results show that there is a clear difference between the expression profiles of group1 and group 2.
Two subgroups of differentially expressed genes were annotated and analyzed for enrichment using an R-package clusterifier, the enrichment content including GO Biological Processes (BP), KEGG Pathways. The differential gene enrichment map is shown in FIG. 10. The results show that the differential genes mainly participate in the pathways such as Notch signaling pathway, MAPK6/MAPK4 signaling pathway, wnt signaling pathway and the like, and the research shows that the differential genes are related to the rectal cancer.
7. COX regression analysis and prediction of prognosis and pathological features using risk scoring
Study m 6 A prognostic role of RNA methylation candidate genes in rectal cancer, univariate analysis of data setAnd (4) Cox regression analysis, namely screening the gene with the obvious p value in the single-factor COX regression analysis as a colorectal cancer prognosis gene, and carrying out the next analysis.
And (3) carrying out risk scoring on each rectal cancer sample, wherein the formula is as follows:
where Coefi is the regression coefficient of COX regression (coefficient) and xi is the expression value of each rectal cancer prognostic gene, this formula is used to calculate the risk score for each rectal cancer sample. Samples were classified into high risk groups and low risk groups according to this risk score. Looking for the difference between the Overall Survivals (OS) between the two classes, the survival graph of the high and low risk group samples is shown in fig. 11. The results showed that 112 of 118 candidate genes were significantly associated with colorectal cancer OS.
Because too many candidate genes which are obtained by screening and are obviously related to the rectal cancer OS are difficult to be used for clinical diagnosis, a rebuilt likelihood-based survival model is constructed to screen characteristic genes, and 10 characteristic genes related to the rectal cancer prognosis are found by using R-enveloped rbsurf and the rebuilt likelihood-based survival model.
The 10 genes and their Cox-p-value results are shown in Table 1.
Table 1: 10 selected survival related characteristic genes
Gene ID | Cox-p-value |
ADAMTSL1 | 0.001766 |
CSMD2 | 3.32E-05 |
FAM13C | 0.000341 |
FAM184A | 8.66E-06 |
KLHL4 | 0.000204 |
OLFML2B | 8.93E-08 |
PDZD4 | 0.000875 |
SEC14L5 | 0.025102 |
SETBP1 | 0.000401 |
TMEM132B | 0.002578 |
8. ROC curve analysis
A Receiver Operating Characteristic (ROC) curve is adopted to estimate the classification performance, and the higher the value of area under the curve (AUC), the higher the classification performance is. The 10 prognostic genes are found to have better area under the ROC curve, and the 10 genes are shown to well reflect the prognosis of the rectal cancer patient.
9. Predicting prognosis and clinicopathologic characteristics of tumor patients using feature-calculated risk scores
From m 6 Obtaining factors which are obviously related to the survival period in the candidate gene A set and constructingThe risk characteristics are that 10 prognostic genes are taken as combined characteristics, are mapped to TCGA-READ, and the risk scores of the combined characteristics are respectively evaluated by using a Support Vector Machine (SVM), so that the prediction effects of the risk scores on the three-year survival rate of tumor patients, the prediction outcome of RM1/2 subgroups, the prognosis results, the stages and the like are evaluated. Wherein TCGA rectal cancer samples were divided into 5 sections, 5-fold cross-validation was applied, the model was trained with four-fifths of the samples and tested on the test set (one-fifth of the samples remaining).
The predicted effect of the risk score for the combined signature on the three-year survival outcome is shown in fig. 12, the risk score for the combined signature on the subgroup is shown in fig. 13, the risk score for the combined signature on the prognostic outcome is shown in fig. 14, and the risk score for the combined signature on the stage is shown in fig. 15. The results show that the marker molecule provided by the invention has good prediction effect on colorectal cancer prognosis.
Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Sequence listing
<110> university of capital medical science
<120> marker molecule associated with colorectal cancer prognosis and detection kit
<130> RYP2010722.4
<160> 10
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1578
<212> DNA
<213> Homo sapiens
<400> 1
atggaatgct gccgtcgggc aactcctggc acactgctcc tctttctggc tttcctgctc 60
ctgagttcca ggaccgcacg ctccgaggag gaccgggacg gcctatggga tgcctggggc 120
ccatggagtg aatgctcacg cacctgcggg ggtggggcct cctactctct gaggcgctgc 180
ctgagcagca agagctgtga aggaagaaat atccgataca gaacatgcag taatgtggac 240
tgcccaccag aagcaggtga tttccgagct cagcaatgct cagctcataa tgatgtcaag 300
caccatggcc agttttatga atggcttcct gtgtctaatg accctgacaa cccatgttca 360
ctcaagtgcc aagccaaagg aacaaccctg gttgttgaac tagcacctaa ggtcttagat 420
ggtacgcgtt gctatacaga atctttggat atgtgcatca gtggtttatg ccaaattgtt 480
ggctgcgatc accagctggg aagcaccgtc aaggaagata actgtggggt ctgcaacgga 540
gatgggtcca cctgccggct ggtccgaggg cagtataaat cccagctctc cgcaaccaaa 600
tcggatgata ctgtggttgc aattccctat ggaagtagac atattcgcct tgtcttaaaa 660
ggtcctgatc acttatatct ggaaaccaaa accctccagg ggactaaagg tgaaaacagt 720
ctcagctcca caggaacttt ccttgtggac aattctagtg tggacttcca gaaatttcca 780
gacaaagaga tactgagaat ggctggacca ctcacagcag atttcattgt caagattcgt 840
aactcgggct ccgctgacag tacagtccag ttcatcttct atcaacccat catccaccga 900
tggagggaga cggatttctt tccttgctca gcaacctgtg gaggaggtta tcagctgaca 960
tcggctgagt gctacgatct gaggagcaac cgtgtggttg ctgaccaata ctgtcactat 1020
tacccagaga acatcaaacc caaacccaag cttcaggagt gcaacttgga tccttgtcca 1080
gccagtgacg gatacaagca gatcatgcct tatgacctct accatcccct tcctcggtgg 1140
gaggccaccc catggaccgc gtgctcctcc tcgtgtgggg ggggcatcca gagccgggca 1200
gtttcctgtg tggaggagga catccagggg catgtcactt cagtggaaga gtggaaatgc 1260
atgtacaccc ctaagatgcc catcgcgcag ccctgcaaca tttttgactg ccctaaatgg 1320
ctggcacagg agtggtctcc gtgcacagtg acatgtggcc agggcctcag ataccgtgtg 1380
gtcctctgca tcgaccatcg aggaatgcac acaggaggct gtagcccaaa aacaaagccc 1440
cacataaaag aggaatgcat cgtacccact ccctgctata aacccaaaga gaaacttcca 1500
gtcgaggcca agttgccatg gttcaaacaa gctcaagagc tagaagaagg agctgctgtg 1560
tcagaggagc cctcgtaa 1578
<210> 2
<211> 10896
<212> DNA
<213> Homo sapiens
<400> 2
atgccgcgct cgcggggacg ggagctgggg cgctgcggct gccccgcggg gagggctcgc 60
ggcgaaaccg ggatttcggc gcttgtgccg ggcgccggga gccgctgggg ccgcccgccg 120
ccgccaacgc cgccgcctct gctgctgttg ctgggctgtg ggttgctcag cgtctcggcc 180
gccgcgggcc agaactgcac gttccaactg cacggtccca atgggacagt tgagagccca 240
gggttcccat atggctaccc caattacgcc aactgcacgt ggaccatcac cgcggaagag 300
cagcacagaa tccagcttgt gttccagtcc tttgccctgg aagaggactt tgatgtcctg 360
tcggtgtttg atggtccacc ccagccagag aatctgcgta cgaggctcac aggctttcag 420
ctgccagcca ccattgttag tgcagccacc accctctctc tgcgcctcat cagcgactat 480
gcagtcagtg cccaaggctt ccacgccacc tatgaagttc tccccagcca cacatgtggg 540
aacccaggga ggctgcccaa tggcatccag cagggttcaa ccttcaacct cggtgacaag 600
gtccgctaca gctgcaacct tggcttcttc ctggagggcc acgccgtgct cacctgccac 660
gctggctctg agaacagcgc cacgtgggac ttccccctgc cttcctgcag agctgatgat 720
gcctgtggtg ggaccctgcg gggccagagt ggcatcatct ccagccccca cttcccctcg 780
gagtaccata acaatgccga ctgcacatgg accatcctgg ctgagctggg ggacaccatc 840
gccctggtgt ttattgactt ccagctggag gatggttacg actttctgga agtcactggg 900
acagaaggct cctccctctg gttcaccgga gccagcctcc cagcccccgt tatcagcagc 960
aagaactggc tgcgactgca cttcacatcg gatggcaacc accggcagcg cggattcagt 1020
gcccaatacc aagtcaagaa gcaaattgag ttgaagtctc gaggtgtgaa gctgatgccc 1080
agcaaagaca acagccagaa gacgtctgtg ttaactcagg ttggtgtgtc ccaaggacat 1140
aatatgtgtc cagaccctgg catacccgaa aggggcaaaa gactaggctc ggatttcagg 1200
ttaggatcca gcgtccagtt cacctgcaac gagggctatg acctgcaagg gtccaagcgg 1260
atcacctgta tgaaagtgag cgacatgttt gcggcctgga gcgaccacag gccagtctgc 1320
cgagcccgca tgtgtgatgc ccaccttcga ggcccctcgg gcatcatcac ctcccccaat 1380
ttccccattc agtatgacaa caatgcacac tgtgtgtgga tcatcacagc actcaacccc 1440
tccaaggtga tcaagctcgc ctttgaggag tttgatttgg agaggggcta tgacaccctg 1500
acggtcggtg atggtggtca ggatggggac cagaagacag ttctctacat cctgacaggt 1560
acatcggtcc cggatctcat tgtcagcacc aatcatcaaa tgtggctcct cttccagact 1620
gatggcagtg gcagttccct gggattcaag gcttcttatg aagagatcga gcagggcagt 1680
tgcggtgacc ctggcatacc tgcatatggc cggagggaag gctcccggtt tcaccacggt 1740
gacacactca agtttgagtg ccagcccgcc tttgagctgg tgggacagaa ggcaatcaca 1800
tgccaaaaga ataaccaatg gtcggctaag aagccaggct gcgtgttctc ctgcttcttc 1860
aacttcacca gcccgtctgg ggttgtcctg tctcccaact acccagagga ctatggcaac 1920
cacctccact gtgtctggct catcctggcc aggcctgaga gccgcatcca cctggccttc 1980
aacgacattg acgtggagcc tcagtttgat ttcctggtca tcaaggatgg ggccaccgcc 2040
gaggcgcccg tcctgggcac cttctcagga aaccagcttc cctcctccat cacaagcagt 2100
ggccacgtgg cccgtctcga gttccagact gaccactcca cagggaagag gggcttcaac 2160
atcactttta ccaccttccg acacaacgag tgcccggatc ctggcgttcc agtaaatggc 2220
aaacggtttg gggacagcct ccagctgggc agctccatct ccttcctctg tgatgaaggc 2280
ttccttggga ctcagggctc agagaccatc acctgcgtcc tgaaggaggg cagcgtggtc 2340
tggaacagcg ctgtgctgcg gtgtgaagct ccctgtggtg gtcacctgac ttcgcccagc 2400
ggcaccatcc tctctccggg ctggcctggc ttctacaagg atgccttgag ctgtgcctgg 2460
gtgattgagg cccagccagg ctaccccatc aaaatcacct tcgacagatt caaaaccgag 2520
gtcaactatg acaccctgga agtacgcgat gggcggactt actcagcgcc cttgatcggg 2580
gtttaccacg ggacccaggt tccccagttc ctcatcagca ccagcaacta cctctacctc 2640
ctcttctcta ccgacaagag tcactcggac atcggcttcc agctccgcta tgagactata 2700
acactgcagt cagaccactg tctggatcca ggaatcccag taaatggaca gcgtcatggg 2760
aatgacttct acgtgggcgc gctggtgacc ttcagctgtg actcgggcta cacattaagt 2820
gacggggagc ctctggagtg tgagcccaac ttccagtgga gccgggccct gcccagttgt 2880
gaagctctct gtggtggctt cattcaaggc tccagtggga ccatcttgtc gccagggttc 2940
cctgacttct accccaacaa cttgaactgc acctggatta tcgaaacatc tcatggcaag 3000
ggtgtgttct tcactttcca caccttccac ctggaaagtg gccatgacta cctcctcatc 3060
actgagaacg gcagcttcac ccagcccctg aggcagctaa ctggatctcg gctgccagct 3120
cccatcagcg ctgggctcta tggcaacttc actgcccagg tccgcttcat ctctgatttc 3180
tccatgtcat atgaaggatt caacatcacc ttctcagagt acgacttgga gccctgtgag 3240
gagcccgagg tcccagccta cagcatccgg aagggcttgc agtttggcgt gggcgacacc 3300
ttgaccttct cctgcttccc cgggtaccgt ctggagggca ccgcccgcat cacgtgcctg 3360
gggggcagac ggcgcctgtg gagctcgcct ctgccaaggt gtgttgctga gtgtgggaat 3420
tcagtcacag gcactcaggg tactttgctg tcccccaact ttcctgtgaa ctacaataac 3480
aatcatgaat gcatctactc catccagacc cagccaggga agggaattca gctgaaagcc 3540
agggcattcg aactctccga aggagatgtc ctcaaggttt atgatggcaa caacaactcc 3600
gcccgtttgc tgggagtttt tagccattct gagatgatgg gggtgacttt gaacagcaca 3660
tccagcagtc tgtggcttga tttcatcact gatgctgaaa acaccagcaa gggctttgaa 3720
ctgcactttt ccagctttga actcatcaaa tgtgaggacc caggaacccc caagtttggc 3780
tacaaggttc atgatgaagg tcattttgca gggagctccg tgtccttcag ctgtgaccct 3840
ggatacagcc tgcggggtag tgaggagctg ctgtgtctga gtggagagcg ccggacctgg 3900
gaccggcctc tgcccacctg tgtcgccgag tgtggaggga cagtgagagg agaggtgtcg 3960
gggcaggtgc tgtcacccgg gtatccagct ccctatgaac acaatctcaa ctgcatctgg 4020
accatcgaag cagaggccgg ctgcaccatt gggctacact tcctggtgtt tgacacagag 4080
gaggttcacg acgtgctgcg catctgggat gggcctgtgg agagcggggt tctgctgaag 4140
gagctgagtg gcccggccct gcccaaggac ctgcatagca ccttcaactc ggtcgtcctg 4200
cagttcagca ctgacttctt caccagcaag cagggctttg ccattcaatt ttcagtgtcc 4260
acagcaacgt cctgcaatga ccctgggatc ccgcagaatg ggagtcggag tggtgacagt 4320
tgggaagccg gcgactccac agtgttccag tgtgaccctg gctacgcgct gcagggaagt 4380
gcagagatca gctgtgtgaa gatcgagaac aggttcttct ggcagcccag cccgccaaca 4440
tgcatcgctc cctgcggggg agacctgaca ggaccatctg gagtcatcct ctcaccaaat 4500
tacccagaac cctacccgcc aggcaaggag tgtgactgga aagtgaccgt ctcaccagac 4560
tacgtcatcg ccctggtatt taacatcttt aacctggagc ctggctatga cttcctccat 4620
atctacgacg gacgggactc tctcagccct ctcataggaa gcttctatgg ctcccagctc 4680
ccaggccgca ttgaaagcag cagcaacagc ctcttcctcg ccttccgcag cgatgcatct 4740
gtgagcaatg ctggcttcgt cattgactat acagaaaacc cgcgggagtc atgttttgat 4800
cctggttcca tcaagaacgg cacacgggtg gggtccgacc tgaagctggg ctcctccgtc 4860
acctactact gccacggggg ctacgaagtt gagggcacct cgaccctgag ctgcatcctg 4920
gggcctgatg ggaagcccgt gtggaacaat ccccggccag tctgcacagc cccctgtggg 4980
ggacagtatg tgggttcgga cggagtggtc ttgtccccca actaccccca gaactacacc 5040
agtggacaga tctgcttgta ttttgttact gtgcccaagg actatgtggt gtttggccag 5100
ttcgccttct ttcacacggc cctcaacgac gtggtggagg ttcacgacgg ccacagccag 5160
cactcgcggc tcctcagctc cctctcgggc tcccatacag gagaatcact gcccttggcc 5220
acctccaatc aagttctcat taagttcagc gccaaaggcc tcgcaccagc cagaggcttc 5280
cactttgtct accaagcggt tcctcgaacc agcgccacgc agtgcagctc tgtgccggaa 5340
ccccgctatg gcaagaggct gggcagtgac ttctcggtgg gggccatcgt ccgcttcgaa 5400
tgcaactccg gctatgccct gcaggggtcg ccagagatcg agtgcctccc tgtgcctggg 5460
gccttggccc aatggaatgt ctcagcgccc acgtgtgtgg tgccgtgtgg aggcaacctc 5520
acagagcgca ggggcaccat cctgtcccct ggcttcccag agccgtacct caacagcctc 5580
aactgtgtgt ggaagatcgt ggtccccgaa ggcgctggca tccagatcca agttgtcagt 5640
tttgtgacag agcagaactg ggactcgctg gaagtatttg atggtgcaga taacactgta 5700
accatgctgg ggagtttctc aggaacaacc gtgcctgccc ttctgaacag cacctccaac 5760
cagctctacc ttcatttcta ctcagatatc agcgtatctg cagctggctt ccacttggag 5820
tacaaaacgg tgggcctgag cagttgtccg gaacctgctg tgcccagtaa cggggtgaag 5880
actggcgagc gctacttggt gaatgatgtg gtgtctttcc agtgtgagcc gggatatgcc 5940
ctccagggcc acgcccacat ctcctgcatg cccggaacag tgcggcgatg gaactaccct 6000
cctccactct gtattgcaca gtgtggggga acagtggagg agatggaggg ggtgatcctg 6060
agccccggct tcccaggcaa ctaccccagt aacatggact gctcctggaa aatagcactg 6120
cccgtgggct ttggagctca catccagttc ctgaacttct ccaccgagcc caaccacgac 6180
tacatagaaa tccggaatgg cccctatgag accagccgca tgatgggaag attcagtgga 6240
agcgagcttc caagctccct cctctccacg tcccacgaga ccaccgtgta tttccacagc 6300
gaccactccc agaatcggcc aggattcaag ctggagtatc aggcctatga acttcaagag 6360
tgcccagacc cagagccctt tgccaatggc attgtgaggg gagctggcta caacgtggga 6420
caatcagtga ccttcgagtg cctcccgggg tatcaattga ctggccaccc tgtcctcacg 6480
tgtcaacatg gcaccaaccg gaactgggac caccccctgc ccaagtgtga agtcccttgt 6540
ggcgggaaca tcacttcttc caacggcact gtgtactccc cggggttccc tagcccgtac 6600
tccagctccc aggactgtgt ctggctgatc accgtgccca ttggccatgg cgtccgcctc 6660
aacctcagcc tgctgcagac agagccctct ggagatttca tcaccatctg ggatgggcca 6720
cagcaaacag caccacggct cggcgtcttc acccggagca tggccaagaa aacagtgcag 6780
agttcatcca accaggtcct gctcaagttc caccgtgatg cagccacagg ggggatcttc 6840
gccatagctt tctccgctta tccactcacc aaatgccctc ctcccaccat cctccccaac 6900
gccgaagtcg tcacagagaa tgaagaattc aatataggtg acatcgtacg ctacagatgc 6960
ctccctggct ttaccttagt ggggaatgaa attctgacct gcaaacttgg aacctacctg 7020
cagtttgaag gaccaccccc gatatgtgaa gtgcactgtc caacaaatga gcttctgaca 7080
gactccacag gcgtgatcct gagccagagc taccctggaa gctatcccca gttccagacc 7140
tgctcttggc tggtgagagt ggagcccgac tataacatct ccctcacagt ggagtacttc 7200
ctcagcgaga agcaatatga tgagtttgag atttttgatg gtccatcagg acagagtcct 7260
ctgctgaaag ccctcagtgg gaattactca gctcccctga ttgtcaccag ctcaagcaac 7320
tctgtgtacc tgcgttggtc atctgatcac gcctacaatc ggaagggctt caagatccgc 7380
tattcagccc cttactgcag cctgcccagg gctccactcc atggcttcat cctaggccag 7440
accagcaccc agcccggggg ctccatccac tttggctgca acgccggcta ccgcctggtg 7500
ggacacagca tggccatctg tacccggcac ccccagggct accacctgtg gagcgaagcc 7560
atccctctct gtcaagctct ttcctgtggg cttcctgagg cccccaagaa tggaatggtg 7620
tttggcaagg agtacacagt gggaaccaag gccatgtaca gctgcagtga aggctaccac 7680
ctccaggcag gcgctgaggc cactgcagag tgtctggaca caggcctatg gagcaaccgc 7740
aatgtcccac cacagtgtgt ccctgtgact tgtcctgatg tcagtagcat cagcgtggag 7800
catggccgat ggaggcttat ctttgagaca cagtatcagt tccaggccca gctgatgctc 7860
atctgtgacc ctggctacta ctatactggc caaagggtca tccgctgtca ggccaatggc 7920
aaatggagcc tcggggactc tacgcccacc tgccgaatca tctcctgtgg agagctcccg 7980
attcccccca atggccaccg catcggaaca ctgtctgtct acggggcaac agccatcttc 8040
tcctgcaatt ccggatacac actggtgggc tccagggtgc gtgagtgcat ggccaatggg 8100
ctctggagtg gctctgaagt ccgctgcctt gccactcaga ccaagctcca ctccattttc 8160
tataagctcc tcttcgatgt actctcttcc ccatccctca ccaaagctgg acactgtggg 8220
actcctgagc ccattgtcaa cggacacatc aatggggaga actacagcta ccggggcagt 8280
gtggtgtacc aatgcaatgc tggcttccgc ctgatcggca tgtctgtgcg catctgccag 8340
caggatcatc actggtcggg caagacccct ttctgtgtgc caattacctg tggacaccca 8400
ggcaaccctg tcaacggcct cactcagggt aaccagttta acctcaacga tgtggtcaag 8460
tttgtttgca accctgggta tatggctgag ggggctgcta ggtcccaatg cctggccagc 8520
gggcaatgga gtgacatgct gcccacctgc agaatcatca actgtacaga tcctggacac 8580
caagaaaata gtgttcgtca ggtccacgcc agcggcccgc acaggttcag cttcggcacc 8640
actgtgtctt accggtgcaa ccacggcttc tacctcctgg gcaccccagt gctcagctgc 8700
cagggagatg gcacatggga ccgtccccgc ccccagtgtc tcttggtgtc ctgtggccat 8760
ccgggctccc cgcctcactc ccagatgtct ggagacagtt atactgtggg agcagtggtg 8820
cggtacagct gcatcggcaa gcgtactctg gtgggaaaca gcacccgcat gtgtgggctg 8880
gatggacact ggactggctc cctccctcac tgctcaggaa ccagcgtggg agtttgcggt 8940
gaccctggga tcccggctca tggcatccgt ttgggggaca gctttgatcc aggcactgtg 9000
atgcgcttca gctgtgaagc tggccacgtg ctccggggat cgtcagagcg cacctgtcaa 9060
gccaatggct cgtggagcgg ctcgcagcct gagtgtggag tgatctcttg tgggaaccct 9120
gggactccaa gtaatgcccg agttgtgttc agtgatggcc tggttttctc cagctctatc 9180
gtctatgagt gccgggaagg atactacgcc acaggcctgc tcagccgtca ctgctcggtc 9240
aatggtacct ggacaggcag tgaccctgag tgcctcgtca taaactgtgg tgaccctggg 9300
attccagcca atggccttcg gctgggcaat gacttcaggt acaacaaaac tgtgacatat 9360
cagtgtgtcc ctggctatat gatggagtca catagagtat ctgtgctgag ctgcaccaag 9420
gaccggacat ggaatggaac caagcccgtc tgcaaagctc tcatgtgcaa gccacctccg 9480
ctcatcccca atgggaaggt ggtggggtct gacttcatgt ggggctcaag tgtgacttat 9540
gcctgcctgg aggggtacca gctctccctg cccgcggtgt tcacctgtga gggaaatggg 9600
tcctggaccg gagagctgcc tcagtgtttc cctgtgttct gcggggatcc tggtgtcccg 9660
tcccgtggga ggagagagga ccgaggcttc tcctacaggt catctgtctc cttctcctgc 9720
catccccctc tggtgctggt gggctctcca cgcaggtttt gccagtcaga tgggacatgg 9780
agtggcaccc agcccagctg catagatccg accctgacca cgtgtgcgga ccctggtgtg 9840
ccacagtttg ggatacagaa caattctcag ggctaccagg ttggaagcac agtcctcttc 9900
cgttgtcaaa aaggctacct gcttcagggc tccaccacca ggacctgcct cccaaacctg 9960
acctggagtg gaaccccacc tgactgtgtc ccccaccact gcaggcagcc agagacgcca 10020
acgcatgcca acgtcggggc cctggatttg ccctccatgg gctacacgct catctactcc 10080
tgccaggagg gcttctccct caagggtggc tccgagcacc gcacctgcaa ggcggatggc 10140
agctggacag gcaagccgcc catctgcctg gaggtccggc ccagtgggag acccatcaac 10200
actgcccggg agccaccgct cacccaagcc ttgattcctg gggatgtttt tgccaagaat 10260
tccctgtgga aaggggccta tgaataccag gggaagaagc agccagccat gctcagagtg 10320
actggcttcc aagttgccaa cagcaaggtc aatgccacca tgatcgacca cagtggcgtg 10380
gagctgcact tggctggaac ttacaagaaa gaagattttc atctcctact ccaggtgtac 10440
cagattacag ggcctgtgga gatctttatg aataagttca aagatgatca ctgggcttta 10500
gatggccatg tctcgtcaga gtcctccgga gccaccttca tctaccaagg ctctgtcaag 10560
ggccaaggct ttgggcagtt cggctttcaa agactggacc tcaggctgct ggagtcagac 10620
cccgagtcca ttggccgcca ctttgcttcc aacagcagct cagtggcagc cgcgatcctg 10680
gtgcctttca tcgccctcat tattgcgggc ttcgtgctct atctctacaa gcacaggaga 10740
agacccaaag ttcctttcaa tggctatgct ggccacgaga acaccaatgt tcgggccaca 10800
tttgagaacc caatgtacga ccgcaacatc cagcccacag acatcatggc cagcgaggcg 10860
gagttcacag tcagcacagt gtgcacagca gtatag 10896
<210> 3
<211> 1464
<212> DNA
<213> Homo sapiens
<400> 3
atgttttctt gtttctgttt cagccttcag gataattcct tcagcagcac cactgtaaca 60
gagtgtgacg aagatccagt ctctctacat gaagaccaga ctgattgctc cagtctcaga 120
gatgaaaaca ataaagagaa ctaccccgac gcaggggctc tggtagaaga gcacgcgccg 180
ccctcttggg agccgcagca gcagaatgta gaggcgaccg tgctggtgga cagcgtattg 240
cgacccagca tgggcaactt caagtccagg aagcccaagt ccatcttcaa agcggagagc 300
gggaggagcc acggagaaag tcaggagaca gagcatgtgg tatccagcca gtcagagtgt 360
caggtgagag caggaacacc agctcatgag agtccacaaa acaatgcctt caagtgccaa 420
gaaacagtgc gacttcaacc aagaatagac cagaggactg ccatttcgcc aaaggatgct 480
tttgaaactc ggcaggactt aaatgaggaa gaagctgctc aggtgcatgg agtcaaggac 540
ccggcgccag catcaaccca gagcgtgctt gccgatggga cagattctgc agacccctca 600
ccagtccaca aagatgggca gaatgaggcc gacagtgcac cagaagacct ccactctgtg 660
gggaccagca ggctgctcta tcacatcact gatggtgata acccactgct gtcgccacga 720
tgctccatct tcagccaaag ccagagattc aacttagacc ccgagtcagc cccatctcca 780
cccagcactc agcagtttat gatgccgcgg agttcttcac gctgcagctg tggagatggc 840
aaggagccac agaccatcac ccagctcacc aagcacatcc agagcctcaa gcggaaaatt 900
cggaaatttg aagaaaaatt tgaacaagaa aagaaatacc gggtaactaa gcaagacaag 960
aacctcataa agccgcttta tgaccgatac agaattatca agcaaatctt gtcaacacct 1020
tcccttattc caacaattca ggaggaagag gactctgatg aagaccgtcc acagggaagc 1080
caacaacctt ctttggcaga tccagcatct caccttcctg ttggtgacca cctcacctac 1140
tctaatgaga ctgagcctgt tagggccctt ttaccagatg aaaagaaaga agtaaaacca 1200
ccagctctct ccatgtctaa tttacatgag gctaccatgc ctgtacttct tgaccatctc 1260
cgagaaacta gggctgacaa gaagagactg cggaaagcct taagagaatt tgaagaacag 1320
ttttttaaac aaacaggaag aagtccacaa aaggaagata ggataccaat ggcagatgag 1380
tattatgaat ataagcacat aaaagccaaa ctgagactat tagaggtcct catcagcaag 1440
caagatgtgg ccaaaactat ttga 1464
<210> 4
<211> 2811
<212> DNA
<213> Homo sapiens
<400> 4
atgaagcagc aggctttgac agaatttgaa gcttataagc acagagttga ggacatgcaa 60
ctttgtgcag aagcccagca tgtccaacgc atagtgacca tgtctagaga agtcgaagag 120
attagaagga aatttgaaga aaaattacgg agctttggac aacttcaagt acagtttgaa 180
aaagacaaac gattggcatt ggaagacttg caagctgctc acagacggga gatacaagag 240
ctattgaagt cacagcagga tcacagtgcc tcagtaaata aaggccagga aaaggcagag 300
gaactacaca gaatggaggt ggagtcccta aacaaaatgc ttgaggagct aagacttgaa 360
cggaagaaac taattgagga ttatgaaggc aagttgaata aagctcagtc cttttatgaa 420
cgtgagcttg atactttgaa aaggtcacag ctttttacag cagaaagcct acaggccagc 480
aaagaaaagg aagctgatct tagaaaagaa tttcagggac aagaagcaat tttacgaaaa 540
actataggaa aattaaagac agagttacag atggtacagg atgaagctgg aagtcttctt 600
gacaaatgcc aaaagcttca gacggcactt gccatagcag agaacaatgt tcaggttctt 660
caaaaacagc ttgatgatgc caaggaggga gaaatggccc tattaagcaa gcacaaagaa 720
gtggaaagtg agctagcagc tgccagagaa cgtttacaac agcaagcttc agatcttgtc 780
ctcaaagcta gtcatattgg aatgcttcaa gcaactcaaa tgacccagga agttacaatt 840
aaagatttag aatcagaaaa atcgagagtc aatgagagat tatctcaact tgaagaggaa 900
agagcttttt tgcgaagcaa aacccaaagt ctggatgaag agcagaagca acagattcta 960
gaactggaga agaaagtaaa tgaagcaaag agaactcagc aagaatatta tgaaagggaa 1020
cttaaaaacc tgcaaagtag attggaagag gaggtgactc aattaaacga ggcccattct 1080
aagactttgg aagaattagc ttggaagcac catatggcaa ttgaagctgt ccacagtaat 1140
gcaattaggg ataagaaaaa actgcaaatg gatttggaag aacaacataa caaagataaa 1200
ctaaacctgg aagaggataa aaatcagctt caacaagagc tagaaaacct aaaggaagta 1260
ctggaagaca agttgaatac agccaatcaa gagattggcc acctccaaga tatggtaagg 1320
aaaagtgaac aaggtcttgg ctctgcagaa ggacttattg ctagtcttca ggactcccag 1380
gaaaggcttc agaatgagct tgacttgact aaagacagcc taaaggagac caaggatgct 1440
ctattaaatg tggagggtga gctagaacaa gaaaggcaac agcatgaaga aacaattgct 1500
gccatgaaag aagaagagaa gctcaaagtg gacaaaatgg cccatgactt agaaattaag 1560
tggactgaaa atcttagaca agagtgttct aaacttcgtg aagagttaag gcttcaacat 1620
gaagaggata agaagtcagc aatgtctcaa cttttgcagt tgaaagatcg agagaaaaat 1680
gcagcaagag attcatggca gaagaaagta gaagatctct taaaccagat ttccttgctg 1740
aaacagaatc tggagataca gctttcccag tctcagactt ctttgcaaca actgcaagcc 1800
cagtttacgc aagaacgaca gcggcttacg caagagcttg aagaattaga ggagcaacat 1860
cagcaaagac acaaatcatt aaaagaagca catgtccttg catttcaaac tatggaagag 1920
gaaaaggaaa aggagcaaag agctcttgaa aatcatttac aacagaagca ttctgcagag 1980
cttcaatcac taaaagatgc acacagagag tcaatggagg gcttccggat agaaatggaa 2040
caggaacttc agactcttcg gtttgaatta gaagatgaag gaaaggctat gcttgcttcc 2100
ttgcgctcag aactcaacca tcaacatgca gctgcaattg atttgttacg gcataatcat 2160
catcaagaat tggcagctgc taaaatggaa ttagagagaa gcatagacat cagcagaaga 2220
cagagtaagg agcacatatg tagaattaca gatctacaag aggaattaag acacagagag 2280
catcacatct ctgaattgga taaggaggtt cagcaccttc atgagaatat aagtgcccta 2340
accaaagaac tggaatttaa ggggaaagaa attctcagaa tacgaagtga atctaaccaa 2400
cagataagat tagaagaaat ggaagaaaaa tatctaatga gagaatcaaa accagaagat 2460
atacagatga ttacagaatt aaaagccatg cttacagaaa gagaccagat cataaagaaa 2520
ctaattcaaa agaagaagaa tgataaatca ccaacaaaca ggtttgtgag tgttcccaat 2580
ctaagtgctc tggaatctgg tggagtgggc aatggacatc ctaaccgcct ggatcccatt 2640
cctaattctc cagtccacga tattgagttc aacagcagca aaccacttcc acagccagtg 2700
ccacctaaag ggcccaagac atttttgagt cctgctcaga gtgaagcttc tccagtggct 2760
tctccagatc cccagcgcca ggagtggttt gcccggtact tcacattctg a 2811
<210> 5
<211> 2163
<212> DNA
<213> Homo sapiens
<400> 5
atgtcagtgt ctggcaagaa agagtttgat gtgaaacaga tcctaaggct acgctggagg 60
tggtttagtc atccttttca aggttccacc aacactggaa gctgtcttca gcaggaagga 120
tatgagcata gagggacccc ggttcagggc aggttgaaga gccactctcg ggacagaaac 180
ggactgaaga aaagcaacag tcctgtccac cacaatatac tggcaccagt gccaggaccg 240
gcccctgccc atcagagagc cgttcagaat ttgcagcaac ataatctgat agtacatttt 300
caagcaaatg aagatactcc taaatcagtt ccagagaaga atttattcaa agaagcttgt 360
gagaaacgcg cacaagattt ggagatgatg gctgatgaca atatagaaga ttctacagca 420
agattagata cacaacactc tgaagacatg aatgccacca gatctgaaga gcagttccat 480
gttataaacc acgcagagca aactcttcgt aaaatggaga actacttgaa agagaaacaa 540
ctatgtgatg tgctactgat tgcaggacac ctccgcatcc cagcccatag gttggttctc 600
agcgcagtgt ctgattattt tgctgcaatg tttactaatg atgtgcttga agccaaacaa 660
gaagaggtca ggatggaagg agtagatcca aatgcactaa attccttggt gcagtatgct 720
tacacaggag tcctgcaatt gaaagaagat accattgaaa gtttgctggc tgcagcttgt 780
cttctgcagc tgactcaggt cattgatgtt tgctccaatt ttctcataaa gcagctccat 840
ccttcaaact gcttagggat tcgatcattt ggagatgccc aaggctgtac agaacttctg 900
aacgtggcac acaaatacac tatggaacac ttcattgagg taataaaaaa ccaagaattc 960
ctcctgcttc cagctaatga aatttcaaaa cttctgtgca gtgatgacat taatgtgcct 1020
gatgaagaga ccatttttca tgctctaatg cagtgggtgg ggcatgatgt gcagaatagg 1080
caaggagaac tggggatgct gctttcttac atcagactgc cattactccc accacagtta 1140
ctggcagatc ttgaaaccag ttccatgttt actggtgatc ttgagtgtca gaagctcctg 1200
atggaagcta tgaagtatca tcttttgcct gagagaagat ccatgatgca aagccctcgg 1260
acaaagccta gaaaatcaac tgtgggggca ctttatgctg taggaggcat ggatgctatg 1320
aaaggtacta ctactattga aaaatatgac ctcaggacca acagttggct acatattggc 1380
accatgaatg gccgtaggct tcaatttgga gtcgcagtta ttgataataa gctctatgtc 1440
gtgggaggaa gagacggttt aaaaactttg aatacagtgg aatgttttaa tccagttggc 1500
aaaatctgga ctgtgatgcc tcccatgtca acacatcggc acggcttagg tgtagccact 1560
cttgaaggac caatgtatgc tgtaggtggt catgatggat ggagctatct aaatactgta 1620
gaaagatggg accctgaggg acgacagtgg aattacgtag ccagtatgtc aactcctaga 1680
agcacagttg gtgttgttgc attaaacaac aaattatatg ctattggtgg acgtgatgga 1740
agttcctgcc tcaaatcaat ggaatacttt gacccacaca ctaacaagtg gagtttgtgt 1800
gctccaatgt ccaaaagacg tggaggtgtg ggagttgcca catacaatgg attcttatat 1860
gttgtagggg ggcatgatgc ccctgcttcc aaccattgct ccaggctttc tgactgtgtg 1920
gaacggtatg atccaaaagg tgattcatgg tcaactgtgg cacctctgag tgttcctcga 1980
gatgctgttg ctgtgtgccc tcttggagac aaactctacg tggttggagg atatgacgga 2040
catacttatt tgaacacagt tgagtcatat gatgcacaga gaaatgaatg gaaagagagc 2100
atgcaagaac ttctacaaaa cttctatacc acacagaagc tgaaagagac tctggggcac 2160
taa 2163
<210> 6
<211> 2253
<212> DNA
<213> Homo sapiens
<400> 6
atggccaagc ctcggctgct agttctctac ttcgctctga ttgtggttcc ggcctgggtg 60
tccagcattg tcctcacagg gacaagcgag cccccagatg cgcagacagt ggcgcctgcg 120
gaggacgaga ctctgcaaaa cgaggcggac aaccaggaga acgttttatc tcagttgctg 180
ggggactatg acaaggtcaa ggctatgtct gagggctcgg actgtcagtg caagtgtgtg 240
gtgagacccc tgggccggga tgcctgccag aggatcaatg cgggggcctc caggaaggaa 300
gacttctata ccgtggaaac catcacctca ggctcgtcgt gcaagtgtgc ctgtgtagca 360
cccccatcgg ccctcaatcc ctgcgaggga gacttcaggc tccagaagct gcgggaggca 420
gacagccagg acttgaagct ctccacaatc atagacatgt tggaaggagc gttctatggc 480
ctggatctcc tgaagctaca ttcagtcacc accaaactgg tggggcgagt ggataaactg 540
gaggaggaag tgtctaaaaa cctcaccaag gaaaatgaac aaatcaaaga ggacatggaa 600
gaaattcgaa ccgagatgaa taagcgaggc aaagaaaatt gctctgaaaa catcctagat 660
agcatgccag acatccgctc agccctgcag agggatgcag cagcagccta cgcccaccca 720
gagtatgaag agcggtttct gcaggaagaa accgtgtccc agcagatcaa ctccatcgaa 780
cttctgcaga cgcgacccct ggctctgcct gaggtggtga agtcacagcg gcccctgcag 840
aggcaggtcc acctgagagg ccggccggcc tcccagccca ctgtcatccg gggcatcacc 900
tactataaag ccaaggtctc tgaagaagag aatgacattg aagagcagca agatgagttt 960
ttcagcggtg acaatggagt ggatttgctg attgaagatc agctcctgag acacaacggc 1020
ctgatgacca gtgtcacccg gaggcctgca gccacccgtc agggacacag cactgctgtg 1080
acaagcgacc tgaacgctcg gaccgcaccc tggtcctcag cactgccaca gccctcgacc 1140
tcagatccca gcatcgccaa ccatgcctca gtgggaccaa cactccaaac aacctcggtg 1200
tctccagatc ccacaaggga gtcagtcctg cagccttctc ctcaggtacc agccaccact 1260
gtggcccaca cagccaccca gcaaccagca gccccagctc ctccggcagt gtctcccagg 1320
gaggcattga tggaagctat gcacacagtc ccagtgcctc ccaccacagt cagaacagac 1380
tcgctgggga aagatgctcc tgctgggtgg ggaacaaccc ctgccagccc cacgctgagc 1440
cccgaagaag aagatgacat ccggaatgtc ataggaaggt gcaaggacac tctctccaca 1500
atcacggggc cgaccaccca gaacacatat gggcggaatg aaggggcctg gatgaaggac 1560
cccctggcca aggatgagcg gatttacgta accaactatt actacggcaa caccctggta 1620
gagttccgga acctggagaa cttcaaacaa ggtcgctgga gcaattccta caagctcccg 1680
tacagctgga tcggcacagg ccacgtggta tacaatggcg ccttctacta caatcgcgcc 1740
ttcacccgca acatcatcaa gtacgacctg aagcagcgct acgtggctgc ctgggccatg 1800
ctgcatgacg tggcctacga ggaggccacc ccctggcgat ggcagggcca ctcagacgtg 1860
gactttgctg tggacgagaa tggcctatgg ctcatctacc cggccctgga cgatgagggc 1920
ttcagccagg aggtcattgt cctgagcaag ctcaatgccg cggacctgag cacacagaag 1980
gagaccacat ggcgcacggg gctccggagg aatttctacg gcaactgctt cgtcatctgt 2040
ggggtgctgt atgccgtgga tagctacaac cagcggaatg ccaacatctc ctacgctttc 2100
gacacccaca ccaacacaca gatcgtcccc aggctgctgt tcgagaatga gtattcctat 2160
acgacccaga tagactacaa ccccaaggac cgcctgctct atgcctggga caatggccac 2220
caggtcactt accatgtcat ctttgcctac tga 2253
<210> 7
<211> 1983
<212> DNA
<213> Homo sapiens
<400> 7
atgggatgta atatgtgcgt ggtccagaaa ccggaggagc agtacaaagt gatgctgcag 60
gaggtggagc tgtataaaag cagccaccgg gacaagctgg gcctgatggt ttgctaccgc 120
acggacgacg aggaggacct gggcatttat gtcggagagg taaatcccaa cagcattgca 180
gccaaagacg gccggatccg tgagggagac cgcatcatcc agattaacgg tgtagacgtc 240
cagaaccggg aagaggcggt ggccatcctg agccaggaag agaacaccaa catctccctg 300
ctggtggccc gacctgagag tcagctggcg aaaaggtgga aggacagcga ccgggatgac 360
ttcctggatg actttggctc tgagaatgag ggggagctgc gtgctcgtaa actgaaatca 420
ccccctgccc agcagcccgg aaacgaagag gagaaggggg ctcccgatgc cggcccaggc 480
ctgagcaaca gccaggagct ggacagcggg gtgggccgga ctgacgagag cacccggaac 540
gaagagagct ctgagcacga cctgctgggg gacgaacccc cgagctccac caacaccccg 600
ggaagcctgc gcaagtttgg cctgcaaggg gacgccctgc agagccggga cttccatttc 660
agcatggact ctctgctggc cgagggggcg gggctgggag ggggcgacgt cccgggcctc 720
acggatgagg agtatgagcg ctaccgtgag ctcctggaga tcaagtgcca cctggagaac 780
ggcaaccagc tgggcctcct ctttccccgg gcctccggag gcaacagcgc cctggacgtc 840
aaccgcaacg agagcctggg ccacgagatg gccatgctgg aggaggagct aaggcacctg 900
gaattcaagt gccgcaacat actgcgggcg cagaagatgc agcagctgcg tgagcgctgc 960
atgaaggcct ggctgctgga ggaggagagc ctctacgacc tggcggccag cgagcccaag 1020
aagcacgagc tgtccgacat ctccgagctg cccgagaagt cggacaagga cagcaccagc 1080
gcctacaaca ctggggagag ctgccgcagc accccgctgc ttgtggagcc cctgcccgag 1140
agccccctgc ggcgggccat ggccggcaac tccaacttga accggacccc tcccggcccc 1200
gctgttgcca cccccgccaa ggcagctcct ccaccgggga gccccgccaa gttccggtcc 1260
ctctcccggg atcctgaggc cggccggagg cagcacgcgg aggagcgcgg ccgccgcaac 1320
cccaagacgg ggttgaccct ggagcgtgtg ggccctgaaa gcagccctta cctctcgcgg 1380
cgccaccgcg gccagggcca ggagggcgag cactaccaca gctgcgtgca gctggccccg 1440
acgcgaggcc tggaggagct gggccacggc cccctgagct tggccggtgg ccctcgggtg 1500
ggcggggtgg cggccgcggc cactgaagca ccgcgcatgg agtggaaagt gaaggtgcgc 1560
agcgacggaa cccgctacgt ggccaagcgg cccgtgcgag atcggctgct gaaagcccgt 1620
gccctgaaga tccgggagga gcgcagcggt atgacgaccg acgacgacgc ggtgagcgag 1680
atgaagatgg gccgctactg gagcaaggag gagcggaagc agcacctgat ccgggcccgt 1740
gagcagcgga agcggcgcga gttcatgatg cagagccggc tggagtgcct gcgggagcag 1800
cagaatggcg acagcaagcc cgagctcaac atcattgccc tgagccaccg caaaaccatg 1860
aagaagcgga acaagaagat cctggacaac tggatcacca tccaggagat gctggcccac 1920
ggcgcgcgct ccgccgatgg caagcgggtc tacaaccctc ttctctcagt caccaccgtg 1980
tga 1983
<210> 8
<211> 2091
<212> DNA
<213> Homo sapiens
<400> 8
atggtgcaaa gataccagtc tcctgtccga gtctacaagt acccgtttga gctggtcatg 60
gcggcctacg agaagcgttt ccccacgtgc ccacagatcc cagtcttcct gggcagcgag 120
gtcttgcgcg agtcccgcag cccggacggg gctgtgcacg tggtggagcg gagctgccgg 180
ctgcgcgtgg acgccccgcg gctgctgcgg aagatcgcag gtgttgagca cgtggtcttc 240
gtgcagacaa acatcttgaa ctggaaggag aggacgctcc tcatcgaagc gcacaatgag 300
accttcgcca accgcgtggt ggtgaacgag cactgcagct acacggtcca ccctgagaat 360
gaagactgga cttgcttcga gcagtctgcc tcactggaca ttcggtcttt ctttggcttt 420
gaaaatgcct tggagaagat cgccatgaag cagtacaccg ccaacgtcaa gagggggaag 480
gaggtgattg agcattacct gaatgagctc atctcccagg gtacctcgca cattccgcgc 540
tggacgcctg ccccagtccg tgaggaggat gcccgcaacc aggctggacc gagggacccc 600
agctccctgg aggcccacgg gccccgtagc accctggggc ccgctctgga ggcggtcagt 660
atggacgggg acaagctgga tgcggactac attgagaggt gcctgggcca cctcacgccc 720
atgcaggaga gctgcctgat ccagcttcgg cactggttac aggagaccca caaaggcaag 780
attcccaaag atgagcacat ccttcggttc ctgcgggctc atgacttcca cctggacaag 840
gcccgggaaa tgctgcgcca gtccttgagc tggcgcaagc agcaccaggt ggatctcctc 900
cttcagacct ggcaaccccc tgccctgctg gaggagttct atgcaggggg ctggcattac 960
caggacatag atggccgccc cctctacatc ctccgcctgg gccagatgga caccaaaggc 1020
ttgatgaagg ccgtggggga ggaggcgctg ctgcggcatg ttctctccgt caacgaggaa 1080
ggacagaagc ggtgtgaggg gagcacaagg cagctgggcc gtcccatcag ctcctggacc 1140
tgcctgctag acctggaggg actcaacatg cggcacctgt ggcggccggg ggtgaaggcc 1200
ctgctgcgga tgattgaggt ggttgaggac aattacccag agaccctggg tcggctgctc 1260
atcgtgcgag ccccccgagt cttccccgtg ctctggacac tgatcagccc cttcatcaat 1320
gagaacacca ggcggaagtt cctcatctac agtggcagca actaccaggg acccggaggc 1380
cttgtggact atctggatag agaagtgatc cctgacttcc ttgggggaga gagtgtgtgt 1440
aatgtccccg aaggagggct ggtccccaag tccctctaca tgacagaaga ggagcaggag 1500
cacacggacc agctgtggca gtggagtgag acctaccatt cagccagcgt gctccgcgga 1560
gccccccacg aggtggccgt ggagatcctg gaaggagagt cggtcatcac ctgggacttt 1620
gacatcctgc gaggggacgt ggtgttcagc ctgtaccaca ccaagcaggc gcccaggctg 1680
ggcgcccggg aaccggggac cagggccagc gggcagctga tcgacaaagg ctgggtcctg 1740
ggcagggatt acagccgtgt ggaggctccc cttgtctgcc gggaggggga gagcatccag 1800
ggctcccatg tgacccggtg gcccggcgtc tacctgctcc agtggcaaat gcacagcccc 1860
cccagcagcg tggcctgcag cctcccgggt gtggacgatg tcctgacggc tctgcacagc 1920
cccgggccca agtgcaaact tctctactac tgtgaggtgc tcgcctctga ggacttcagg 1980
ggctccatgt ccagcctgga atcctgcacc agcggcttct cccagctcag cgccgccacc 2040
tcgtcctcct cctccggcca gtctcatagc agctccctgg tctccagata g 2091
<210> 9
<211> 4791
<212> DNA
<213> Homo sapiens
<400> 9
atggagtcca gggaaacctt aagcagctcc cggcaaagag ggggcgagtc agacttcctg 60
ccggtctcct cagccaagcc cccagctgct cctggctgtg caggagaacc tttgctctcc 120
actccaggac ctgggaaggg gatcccggtg ggcggagagc gcatggagcc agaggaggag 180
gatgaactag gctcagggcg ggatgtggat tccaactcca acgcggacag tgagaaatgg 240
gtggcaggag atggtttgga agagcaggaa ttttctatca aggaggcaaa cttcacagag 300
ggaagtctga agctaaagat tcagaccaca aagcgggcta agaaaccccc aaagaatttg 360
gagaactata tatgtccacc tgagatcaag atcaccatca agcagtctgg ggaccagaag 420
gtgtcccgtg ctggaaaaaa tagcaaagcc acgaaggagg aagaaagaag ccactccaaa 480
aagaagctcc tcacagccag tgaccttgca gccagtgacc tcaaaggatt tcagccacag 540
gcttacgaga ggccccagaa acattcaact ctccattatg acacgggcct cccacaggac 600
ttcaccggtg acaccttaaa accaaagcac cagcaaaaaa gcagcagcca gaaccacatg 660
gactggtcca ccaactctga cagcggaccc gtcactcaga attgcttcat cagtccagag 720
tctggcagag aaactgcaag caccagcaag atccccgctc ttgagcccgt ggcttccttt 780
gcaaaggccc agggtaagaa aggcagtgca gggaacacgt ggagtcagtt gtctaacaat 840
aacaaagatc tgctcttggg aggtgtggct ccatccccaa gcagccacag ctcaccagcc 900
ccacccagca gctctgctga gtgcaacggg cttcagccct tggtggatca agatggagga 960
ggtacaaagg agcccccaga accacctacg gtgggcagca agaaaaagtc cagtaaaaaa 1020
gatgtgataa gtcagaccat accaaaccca gacctggatt gggtcaagaa tgcccagaaa 1080
gcatttgaca atacagaagg gaaaagggaa ggttattccg cagatagtgc ccaagaggca 1140
tcaccagcca ggcagaacgt gagttctgcc agtaatcctg aaaatgactc aagtcatgtc 1200
cggattacta tccccatcaa ggcaccctct ctggatccaa ccaaccataa gaggaaaaaa 1260
agacagtcca ttaaagcggt ggtggaaaag atcatgccag agaaagcctt ggcttctgga 1320
atcaccatga gcagtgaagt agttaacagg atactttcca actctgaggg gaataagaag 1380
gatccccgtg tccctaagtt gagtaaaatg atagagaatg agtccccctc agttggcctt 1440
gaaactggtg gaaatgctga gaaagttatc ccaggaggtg tgtctaagcc gcggaagcca 1500
cccatggtca tgacacctcc aacgtgcaca gatcactctc catccagaaa gctgccagaa 1560
atccagcatc caaaatttgc tgcaaaacga aggtggactt gcagcaaacc aaaacctagc 1620
accatgcttc gagaggcagt tatggccacc tctgataaac tgatgctgga gcccccgtct 1680
gcatatccca tcaccccatc cagccctctc tacaccaaca cagacagtct tactgtgatc 1740
actccagtca aaaagaagcg gggacgacca aagaagcagc ctttgctcac agtcgagacg 1800
attcatgagg gaacttccac cagccccgtc agtcccatca gccgagagtt tcctggcact 1860
aagaaaagaa agcgacgacg caatttagcg aagttggccc agctagtgcc gggagaggac 1920
aaacccatga gcgagatgaa atttcacaag aaagttggaa agctcggcgt gttggataag 1980
aagaccatca aaactatcaa taagatgaag acactcaaga ggaaaaacat cttgaatcag 2040
atcttgtcct gttccagcag cgttgctctg aaggcaaaag ctcccccaga gaccagccct 2100
ggggcagcag ccattgaaag caaactgggc aagcagatta atgtcagcaa gaggggaacc 2160
atctacattg gcaagaagcg gggcaggaag ccaagagcag agctgccacc cccatccgaa 2220
gaacccaaaa cagccatcaa gcaccccagg cctgtttcta gccagccgga tgttccagcc 2280
gtgccttcca actttcagtc acttgtggcg tcttcaccag cagctatgca cccactttca 2340
acacagttag gtgggtccaa tggcaacctg agccctgcca gcactgaaac caatttttca 2400
gagttgaaaa ctatgccaaa tctccagccc atcagtgctc ttccaaccaa aacccaaaag 2460
ggaatacaca gtggaacctg gaagctgtct ccacccagac tgatggccaa ctccccttca 2520
cacctgtgcg agattggctc cctaaaggaa atcacgctgt cccctgtgag cgagtcccac 2580
agtgaggaga cgatccccag cgacagcggc attgggacag acaacaacag cacttctgac 2640
caagcggaga agagctcaga atcccgaagg aggtactctt ttgatttctg ctccctggac 2700
aacccggagg ccattccgtc cgacaccagc acaaagaacc ggcatggcca ccggcaaaag 2760
catctcattg tggacaactt tctggcccac gaaagcctca agaagccaaa gcacaagagg 2820
aaacggaaaa gcctgcaaaa ccgcgatgac ctccagtttc tggcagacct ggaggagcta 2880
atcaccaagt tccaagtgtt cagaatctcc caccggagtt acaccttcta ccacgagaat 2940
ccatatccca gcatttttcg gattaatttt gatcactatt acccggtgcc atatatccag 3000
tatgacccgt tgctctatct tcgtaggact tcagacttga agtcaaagaa gaagcgtggt 3060
aggcctgcaa aaaccaatga caccatgaca aaggtgcctt ttttacaagg gttcagctac 3120
cctattccca gtggaagtta ctatgcaccc tatggaatgc cttacacatc aatgcctatg 3180
atgaaccttg gttattacgg tcagtaccca gctcctttgt acctatcgca cacgcttgga 3240
gcagcttccc cattcatgag gccaacagtg ccaccacctc agttccacac aaactcccac 3300
gtaaagatgt ccggtgcagc taagcataaa gccaagcatg gagtacacct gcagggacct 3360
gttagcatgg gccttggtga catgcagcct tctctgaacc ctcccaaggt aggcagtgcc 3420
agtctgtcca gtggtcggct ccataagagg aaacacaaac acaagcataa gcacaaggaa 3480
gaccggatcc tagggaccca tgacaacctg agtggtcttt ttgcaggcaa agccacaggc 3540
ttctccagcc acatcctgag cgagcggctg agtagcgcag acaaagagct cccgctggtg 3600
agtgagaaga acaagcataa ggagaaacag aagcaccagc acagcgaagc cggccacaaa 3660
gcttctaaga acaactttga ggtggacacc ctgtctacac tgtcactttc cgacgcccag 3720
cattggacac aggccaagga aaaaggagac ttgagcagtg agcctgtgga ctcatgcacg 3780
aaaagatact ctggcagtgg cggggatggt ggcagcacga gatcagagaa cctggacgtg 3840
ttcagtgaaa tgaacccttc gaatgacaag tgggacagtg acgtgagtgg gagtaaaagg 3900
aggagctatg aaggctttgg aacgtacagg gaaaaggaca tccaagcctt caagatgaac 3960
cgcaaggaga gaagttctta tgactcctcc atgtctccag ggatgccaag tccccactta 4020
aaagtggacc agacagcagt gcatagtaag aacgaaggct cagtgcccac catgatgacc 4080
aggaagaagc cagccgcagt tgacagtgtt acaattccac cagccccagt gttatctctc 4140
cttgctgcat ctgcagcaac gtcggatgca gtcggctcct ccctgaagaa gaggttcaag 4200
cggcgggaga tcgaagccat ccagtgcgaa gtgcggaaga tgtgcaacta caccaagatc 4260
ctgtccacca agaagaacct ggaccacgtg aacaagatcc tgaaggccaa gcggctgcag 4320
agacaatcaa aaacaggcaa caacttcgtg aagaagaggc gcgggcgtcc caggaagcag 4380
cccacccagt tcgatgagga ctccagagac caaatgccgg tgctggaaaa atgcatcgac 4440
ctgcccagca aaagaggcca gaagcccagc ctgagcccgc tggtgctgga gcccgccgcc 4500
agccaagaca ccatcatggc caccatcgag gcggtcatcc acatggcccg ggaggcgccg 4560
cccctgcccc cgccaccgcc gccgcccctg ccgccaccgc cgccaccacc cctgcccccg 4620
ccaccccctc tacccaagac cccccgaggc ggaaagagga aacacaaacc gcaggccccc 4680
gctcagcccc cacagcagtc gcccccgcag cagccccttc cccaggaaga ggaggtgaaa 4740
gccaaaaggc agaggaagtc ccgagggagt gagagcgagg tccttcccta g 4791
<210> 10
<211> 1773
<212> DNA
<213> Homo sapiens
<400> 10
atgaagagca aagtggacac gattgtgaac ttcacccacc agcacttcac ctcccagttc 60
gaggtcactg tctgggcacc caggctcccc ctgcagattg agatctcaga caccgagctg 120
agccagatca agggctggag gatcccggtt gctgccaaca gaaggcctac ccgggaaagc 180
gatgacgagg acgatgagga gaagaaggga cgaggctgct ccctgcagta ccagcacgcc 240
acagtgcgtg tcctcaccca gtttgtggcc gagtcacctg acttagggca gctgacctac 300
atgctgggcc ccgactggca gtttgacatc actgaccttg tgaccgagtt catgaaggtg 360
gaggagccga aaatcgctca gttacaggac ggcaggaccc tggctggtcg ggagccggga 420
ataaccacgg tgcaggtcct ctcgccgttg tctgactcca tcctggctga gaagacggtg 480
attgtcctgg atgaccgagt caccatcgcg gagctgggag tgcagctcgt agctggcatg 540
tctctctccc tgcagccaca ccgagcagac aaaagggcca tcgtctccac agctgctgcc 600
ctggatgttc ttcagtcccc acagcaggaa gcaatagtaa gttcttggat tttgttcagt 660
gatggttcgg tgacaccttt agacatttac gatcctaagg attattctgt tactgtctca 720
tcattggatg aaatggtggt gtctgtccag gcaaaccttg agtccaaatg gccaattgtg 780
gttgcagagg gtgaaggaca agggcctttg attaagttag aaatgatgat aagtgaacct 840
tgtcagaaga ccaagaggaa gagtgttctt gccgtgggta aaggaaatgt caaggtcaaa 900
ttcgaaccaa gtagtgatga gcaccaagga ggcagcaatg atattgaggg cataaatcgg 960
gaatataaag accacctcag taattccata gagcgcgaag gaaaccagga gagagcagtc 1020
caggaatggt tccaccgtgg cacacctgtt ggccaagagg aaagtaccaa caaaagcaca 1080
accccccagt ctcccatgga agggaagaat aagttactca aaagtggtgg tccagatgcc 1140
tttacaagct tccccactca agggaagtca ccggacccca ataatcctag tgacctcaca 1200
gtgacctcaa gggggctaac ggacttggag attggcatgt atgccttgct ctgcgtcttc 1260
tgtctggcca ttctggtctt cttgatcaac tgcgtggcgt ttgcctggaa atacagacac 1320
aaaaggtttg ctgtgagtga gcagggcaac atcccccatt cccacgactg ggtctggctt 1380
gggaatgaag tggaactttt ggagaaccct gttgacatta cactcccatc agaggagtgc 1440
acaaccatga tagacagggg cctgcagttc gaggagagga acttccttct gaatggcagt 1500
tcccagaaga cttttcatag tcaactactc agaccctctg actatgtcta tgagaaagaa 1560
attaaaaatg aacctatgaa ttcttcgggc ccaaagagga agagagtcaa gttcacttcc 1620
tacaccacca tcctcccaga ggacggcggc ccatacacca actccatcct gtttgacagc 1680
gatgataaca tcaagtgggt ctgccaagat atggggctgg gggattcaca ggactttaga 1740
gactatatgg aaagtctgca agaccagatg taa 1773
Claims (7)
1. The marker molecule related to the colorectal cancer prognosis is characterized by comprising gene sequences shown as SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9 and SEQ ID NO. 10.
2. A test kit for assessing the prognostic effect of rectal cancer, comprising: reagents for detecting marker molecules associated with the prognosis of rectal cancer; the marker molecule comprises gene sequences shown as SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9 and SEQ ID NO 10.
3. The kit of claim 2, wherein the reagents for detecting the marker molecule comprise a primer pair for the marker molecule.
4. The kit of claim 3, wherein the reagents for detecting the marker molecule comprise a fluorescent probe specific for the marker molecule.
5. A system for assessing the prognostic effect of rectal cancer, the system comprising:
(1) The data input module is used for inputting the content detection result of the marker molecules related to the prognosis of the rectal cancer into the model calculation module;
the marker molecule comprises gene sequences shown as SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9 and SEQ ID NO 10;
(2) The model calculation module is used for calculating and processing the input content detection result to obtain the prognosis effect data of the detected patient;
(3) And the result output module is used for evaluating the prognosis effect data of the detected patient according to the evaluation standard of the prognosis effect of the rectal cancer and outputting an evaluation result.
6. Use of the marker molecule of claim 1 for the preparation of a diagnostic agent for rectal cancer.
7. Use of the marker molecule of claim 1 for the preparation of a reagent for the prognostic evaluation of a patient having rectal cancer.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010915926.9A CN112029860B (en) | 2020-09-03 | 2020-09-03 | Marker molecule related to colorectal cancer prognosis and detection kit |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010915926.9A CN112029860B (en) | 2020-09-03 | 2020-09-03 | Marker molecule related to colorectal cancer prognosis and detection kit |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112029860A CN112029860A (en) | 2020-12-04 |
CN112029860B true CN112029860B (en) | 2022-11-22 |
Family
ID=73591841
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010915926.9A Active CN112029860B (en) | 2020-09-03 | 2020-09-03 | Marker molecule related to colorectal cancer prognosis and detection kit |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112029860B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113337605B (en) * | 2021-05-28 | 2022-06-07 | 首都医科大学 | Marker molecules associated with gastric cancer prognosis |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010033371A2 (en) * | 2008-09-22 | 2010-03-25 | Advpharma, Inc. | Molecular markers for lung and colorectal carcinomas |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101255769B1 (en) * | 2010-12-16 | 2013-04-19 | (주)지노믹트리 | Method for Detecting Methylation of Colorectal Cancer Specific Methylation Marker Gene for Colorectal Cancer Diagnosis |
US9752197B2 (en) * | 2010-12-16 | 2017-09-05 | Genomictree, Inc. | Method for detecting methylation of colorectal cancer specific methylation marker gene for colorectal cancer diagnosis |
EP3688195A1 (en) * | 2017-09-27 | 2020-08-05 | Cambridge Epigenetix Limited | Biomarkers for colorectal cancer detection |
US20200017906A1 (en) * | 2018-02-12 | 2020-01-16 | Sun Yat-Sen University | Use of pirna-54265 in diagnosis, treatment, and prognostic evaluation of colorectal cancer |
CN109486948A (en) * | 2018-10-16 | 2019-03-19 | 温州医科大学 | The polymolecular marker and its device and evaluation method of a kind of individuation prediction colorectal cancer prognosis of function-driven |
CN109504778B (en) * | 2019-01-11 | 2021-11-09 | 复旦大学附属中山医院 | 5hmC multi-molecular marker based on apparent modification and colorectal cancer early diagnosis model |
CN110283908B (en) * | 2019-06-04 | 2021-01-15 | 华中科技大学 | Colorectal cancer auxiliary diagnosis SNP marker and application thereof |
-
2020
- 2020-09-03 CN CN202010915926.9A patent/CN112029860B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010033371A2 (en) * | 2008-09-22 | 2010-03-25 | Advpharma, Inc. | Molecular markers for lung and colorectal carcinomas |
Also Published As
Publication number | Publication date |
---|---|
CN112029860A (en) | 2020-12-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10138520B2 (en) | Diagnostic miRNA markers for Alzheimer | |
JP2022050571A (en) | Methods for assessing risk of disease occurrence or recurrence using expression level and sequence variant information | |
AU2012352153B2 (en) | Cancer diagnostics using non-coding transcripts | |
ES2692333T3 (en) | Resolution of genome fractions using polymorphism count | |
CA3180334A1 (en) | Methods for detection of donor-derived cell-free dna | |
CN107206043A (en) | The system and method for diagnosing idiopathic pulmonary fibrosis on transbronchial biopsy using machine learning and higher-dimension transcript data | |
CN106459961A (en) | Pancreatic cancer detection kit, device, and detection method | |
CA2897828A1 (en) | Methods for identifying, diagnosing, and predicting survival of lymphomas | |
CN101506379A (en) | Detection method | |
US20220177976A1 (en) | Colorectal cancer screening method and device | |
CN104619840A (en) | Fgfr2 fusion gene | |
CN104968802B (en) | New miRNA as diagnosis marker | |
Dong et al. | Population-level variation in enhancer expression identifies disease mechanisms in the human brain | |
CN110198711A (en) | Method for detecting cancer | |
CN115443341A (en) | Method for analyzing cell-free nucleic acid and application thereof | |
EP3146074A1 (en) | Diagnosis of neuromyelitis optica vs. multiple sclerosis using mirna biomarkers | |
CN109666745A (en) | The detection method and kit of chromosome 1p/19q joint loss of heterozygosity | |
US20200176081A1 (en) | Method for detecting gene rearrangement by using next generation sequencing | |
CN112029860B (en) | Marker molecule related to colorectal cancer prognosis and detection kit | |
US20210071264A1 (en) | Expression and genetic profiling for treatment and classification of dlbcl | |
CN113981071A (en) | CSF1R related gene mutation as marker for diagnosing CVM and application thereof | |
US20220084632A1 (en) | Clinical classfiers and genomic classifiers and uses thereof | |
WO2020194057A1 (en) | Biomarkers for disease detection | |
CN110358835A (en) | Application of the biomarker in gastric cancer is detected, diagnosed | |
KR101985864B1 (en) | Composition for detecting Breast Cancer and Ovarian Cancer and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |