CN109385478A - The genetic marker for detecting 19-GCS is preparing the application in the product for diagnosing early stage adenocarcinoma of lung prognosis - Google Patents
The genetic marker for detecting 19-GCS is preparing the application in the product for diagnosing early stage adenocarcinoma of lung prognosis Download PDFInfo
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Abstract
The invention discloses the genetic markers of 19-GCS to prepare the application in the product for diagnosing early stage adenocarcinoma of lung prognosis.Claimed application of the product in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma for obtaining 19-GCS scoring.The subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk, and the prognosis of low-risk is better than high risk.In 19-GCS scoring=subject lung cancerous tissue the abundance of 8 positive regulating genes and in value-subject lung cancerous tissue 11 negative regulator genes and value.8 positive regulating genes: ST14, RDH14, DARS, CTSL2, C16orf88, ARL6IP1, SLC6A10P, MEX3D.11 negative regulator genes: SERPINB6, FAM162B, PARK2, GPX3, HLA-DQB1, HOXA2, LOC100128288, RPL13AP17, SETDB2, SLC5A4, LRP2BP.The present invention has major application promotional value for the prognosis of the early stage of lung cancer.
Description
Technical field
The present invention relates to the genetic markers of detection 19-GCS in preparing the product for diagnosing early stage adenocarcinoma of lung prognosis
Using.
Background technique
Adenocarcinoma of lung (lung adenocarcinoma) is one kind of lung cancer, belongs to non-small cell carcinoma.Adenocarcinoma of lung is originating from branch
Tunica mucosa tracheae epithelium, minority originate from lesser bronchus originating from big bronchial muccus gland, most gland cancer, are peripheral lung
Cancer.Adenocarcinoma of lung early stage typically no apparent clinical symptoms, are often found in chest X-ray, show as round or ellipse
Circular lump.
Operation excision is the main treatment means of early stage adenocarcinoma of lung, and the unique method of clinical cure lung cancer at present.Lung
Cancer operation is divided into radical surgery and palliative operation, should strive radical excision, swollen to reach best, thorough excision
Tumor reduces metastases and recurrence.
Summary of the invention
The object of the present invention is to provide the genetic markers of 19-GCS to prepare the product for diagnosing early stage adenocarcinoma of lung prognosis
In application.
Application of the claimed product first in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma；It is described
Product first is the product for detecting 19 specific genes；
The present invention also protect the product first and record the carrier of method first -1 preparation to early stage patients with lung adenocarcinoma into
Application in the system of row prognosis；
Method first -1 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk,
The prognosis of low-risk is better than high risk.
The present invention also protect the product first and record the carrier of method first -2 preparation to early stage patients with lung adenocarcinoma into
Application in the system of row prognosis；
Method first -2 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is subject lung cancerous tissue
In 8 positive regulating genes abundance and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk,
The prognosis of the poor prognosis of high risk, low-risk is excellent.
Application of the product second in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma is also claimed in the present invention；Institute
Stating product second is the product for detecting the abundance of 19 specific genes in subject lung cancerous tissue.
The present invention also protect the product second and record the carrier of method second -1 preparation to early stage patients with lung adenocarcinoma into
Application in the system of row prognosis；
Method second -1 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk,
The prognosis of low-risk is better than high risk.
The present invention also protects the product second preparing with the carrier for recording method second -2 to early stage patients with lung adenocarcinoma
Carry out the application in the system of prognosis；
Method second -2 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is subject lung cancerous tissue
In 8 positive regulating genes abundance and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk,
The prognosis of the poor prognosis of high risk, low-risk is excellent.
Application of the product third in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma is also claimed in the present invention；Institute
Stating product third is the product for obtaining 19-GCS scoring.
The present invention also protects the product third preparing with the carrier for recording judgment criteria -1 to early stage patients with lung adenocarcinoma
Carry out the application in the system of prognosis；The judgment criteria -1 are as follows: the subject of 19-GCS scoring ﹤ threshold value is low-risk, 19-
GCS scoring >=threshold value subject is high risk, and the prognosis of low-risk is better than high risk.
The present invention also protects the product third preparing with the carrier for recording judgment criteria -2 to early stage patients with lung adenocarcinoma
Carry out the application in the system of prognosis；The judgment criteria -2 are as follows: the subject of 19-GCS scoring ﹤ threshold value is low-risk, 19-
GCS scoring >=threshold value subject is high risk, and the prognosis of the poor prognosis of high risk, low-risk is excellent.
The present invention also protects a kind of system, and purposes is to carry out prognosis to early stage patients with lung adenocarcinoma；The system is system
First or system second or system third.
The system first includes the product first.The system first further includes being loaded with the method first -1 or the method
The carrier of first -2.
The system second includes the product second.The system second further includes being loaded with the method second -1 or the method
The carrier of second -2.
The system third includes the product third.The system third further includes being loaded with the judgment criteria -1 or described sentencing
The carrier of disconnected standard -2.
19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is the rich of 8 positive regulating genes in subject lung cancerous tissue
Degree and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value.
19 specific genes are following 19 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene, SERPINB6 gene, FAM162B gene,
PARK2 gene, GPX3 gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene,
SETDB2 gene, SLC5A4 gene, LRP2BP gene.
8 positive regulating genes are following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene.
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
Any description above system is kit or detection platform.
Any description above subject is early stage patients with lung adenocarcinoma.
The early stage adenocarcinoma of lung is I phase adenocarcinoma of lung.
Any description above threshold value is 53.41.
The abundance of 19 specific genes is concretely in any description above lung cancerous tissue: 19 in lung cancerous tissue RNA
The abundance of a specific gene.
Any description above abundance is concretely: using the RNA of subject lung cancerous tissue as sample, passing through
IlluminaHiseq platform is carried out after the original value that high-flux sequence obtains is standardized with software kit with NGS technology
Numerical value.
The prognosis is for (a) and/or (b):
(a) survival rates of the patient of low-risk are higher than the patient of high risk；
(b) the postoperative new hair tumor risk of the patient of low-risk is lower than the patient of high risk.
The prognosis of the low-risk is presented as (a) and/or (b) better than high risk:
(a) survival rates of the patient of low-risk are higher than the patient of high risk；
(b) the postoperative new hair tumor risk of the patient of low-risk is lower than the patient of high risk.
The prognosis is excellent to be presented as (a) and/or (b):
(a) survival rates are high；
(b) postoperative new hair tumor risk is low.
The poor prognosis is presented as (a) and/or (b):
(a) survival rates are low；
(b) postoperative new hair tumor risk is high.
The survival rate is postoperative 1 year survival rate or postoperative 2 years survival rates or postoperative triennial deposits rate or postoperative 5 years survive
Rate.
The present invention has major application promotional value for the prognosis of early stage adenocarcinoma of lung.
Detailed description of the invention
Fig. 1 is the recurrence-free survival rate of the high risk group and low-risk group of 19-GCS in each training set
Kaplan-Meier curve (the 1st group to the 6th group).
Fig. 2 is the recurrence-free survival rate of the high risk group and low-risk group of 19-GCS in each training set
Kaplan-Meier curve (the 7th group to the 10th group).
Fig. 3 is the recurrence-free survival rate of the high risk group and low-risk group of 19-GCS in each test set
Kaplan-Meier curve (the 1st group to the 6th group).
Fig. 4 is the recurrence-free survival rate of the high risk group and low-risk group of 19-GCS in each test set
Kaplan-Meier curve (the 7th group to the 10th group).
The Kaplan- of the high risk group that Fig. 5 is 19-GCS and the recurrence-free survival rate that low-risk group is concentrated in total case
Meier curve.
The high risk group and low-risk group that Fig. 6 is 19-GCS are bent in the Kaplan-Meier for the overall survival that total case is concentrated
Line.
Fig. 7 be Okayama collect case library in 19-GCS high risk group and low-risk group recurrence-free survival rate and
The Kaplan-Meier curve of overall survival.
Fig. 8 is the Progression free survival rate of the high risk group and low-risk group of 19-GCS in the case library of Shedden collection
Kaplan-Meier curve.
Fig. 9 is the Kaplan- of the overall survival of the high risk group and low-risk group of 19-GCS in the case library of Tang collection
Meier curve.
Figure 10 is to be scored according to first therapeutic effect grouped comparison 19-GCS.
Figure 11 is whether to have tumor grouped comparison 19-GCS scoring of newly swelling after basis is treated for the first time.
Figure 12 is to compare 19-GCS scoring according to tumor type packet of newly swelling.
Figure 13 is to be scored according to follow-up care effect grouped comparison 19-GCS.
Figure 14 is the ratio statistical result of follow-up 5 years tumors of newly swelling in embodiment 2.
Figure 15 is the result of 5 years overall survivals of follow-up statistics in embodiment 2.
Specific embodiment
Embodiment below facilitates a better understanding of the present invention, but does not limit the present invention.Experiment in following embodiments
Method is unless otherwise specified conventional method.Test material as used in the following examples is unless otherwise specified certainly
What routine biochemistry reagent shop was commercially available.Quantitative test in following embodiment is respectively provided with three repeated experiments, as a result makes even
Mean value.
The foundation of embodiment 1, the method for 19-GCS diagnosis early stage adenocarcinoma of lung
It collects early stage adenocarcinoma of lung related gene data in U.S.'s tumour database (TCGA database), delivered in document early
The early stage adenocarcinoma of lung related gene data of phase adenocarcinoma of lung related gene data and clinical discovery.It obtains altogether and 17334 morning
Phase adenocarcinoma of lung related gene.
The sample information of 275 patients of I phase adenocarcinoma of lung in TCGA database is randomly selected 35% as test set
(test sets, n=97), 65% is used as training set (training sets, n=178), has been randomly assigned different 10 groups altogether
It is (top 25%expression) and low to be divided into high expression by test set and training set for the expression of each of each group gene
It expresses (bottom 25%expression), each gene P relevant to RFS prognosis in every group is calculated by Cox analysis meter
Value, take statistically significant gene i.e. relevant to RFS, obtained in this 10 groups of training sets minimum 541, it is 1696 most
Significant gene, wherein there is 19 genes to exist jointly in this 10 groups of significant genes.
The combination of 19 genes of acquisition is named as 19-GCS (19gene consensus signature) gene mark
Note.
Positive regulating gene is 8, and species are Homo sapiens (human), and specifying information is shown in Table 1.Negative regulator gene
It is 11, species are Homo sapiens (human), and specifying information is shown in Table 2.
Table 1
Table 2
By the abundance of 8 positive regulating genes, (illuminaHiseq platform carries out what high-flux sequence obtained with NGS technology
Original value be standardized with software kit after numerical value) be added, obtain numerical value A.By the abundance of 11 negative regulator genes
(illuminaHiseq platform is carried out after the original value that high-flux sequence obtains is standardized with software kit with NGS technology
Numerical value) it is added, obtain numerical value B.Numerical value B is subtracted with numerical value A, obtains 19-GCS scoring.
The Kaplan-Meier curve of recurrence-free survival rate of the 19-GCS scoring in each group of training set is shown in Fig. 1 and Fig. 2,
Related data is shown in Table 1.The Kaplan-Meier curve of recurrence-free survival rate of the 19-GCS scoring in each group of test set is shown in Fig. 3
And Fig. 4, related data are shown in Table 2.In Fig. 1, Fig. 2, Fig. 3 and Fig. 4, solid line lines represent the low-risk divided based on 19-GCS scoring
Group, dashed lines represent the high risk group divided based on 19-GCS scoring.The result shows that 19-GCS high risk and low-risk group exist
The Kaplan-Meier curve of recurrence-free survival rate in each group of training set and test set, there is statistical difference.
Table 1
Table 2
The scoring of 19-GCS genetic marker is calculated, thermal map shows increasing with scoring, increasing of the risk also with scoring
High and increase, 235 are low-risk case in 275 patients of I phase adenocarcinoma of lung, and 40 are high risk case, but high risk disease
The recurrence rate in example area will be apparently higher than low-risk area.The high risk group of 19-GCS and the recurrence-free survival rate (RFS) of low-risk group
Kaplan-Meier curve see Fig. 5.The Kaplan- of the overall survival (OS) of the high risk group and low-risk group of 19-GCS
Meier curve is shown in Fig. 6.OS and RFS of the high risk group and low-risk group of 19-GCS in entire I phase patients with lung adenocarcinoma have difference
It is different, and it is respectively suitable for adenocarcinoma of lung IA phase and adenocarcinoma of lung IB phase, compared with normal tissue, the 19-GCS scoring of tumor tissues is obvious
Increase.
Multiplicity prompt 19-GCS is the independent prognostic factor of OS and RFS.
Each gene information and sample information are obtained respectively from several databases of NCBI GEO, verify the reality of 19-GCS
With property, Fig. 7, Fig. 8 and Fig. 9 are seen.In Fig. 7, Fig. 8 and Fig. 9, Low-Risk represents low-risk group, and High-Risk represents high risk
Group.19-GCS equally has prognostic value, and Kaplan-Meier curve shows that the OS and RFS of high risk and low-risk group have significantly
Difference.
Compare the relevant difference with high risk and low-risk with Wilcox test and the FDR correction
Gene, choosing FDR < 0.01 is standard, filters out 777 genes altogether, passes through KEGG, WikiPathways and Reactome access
Enrichment analysis, prompts 7 special relevant accesses, is respectively as follows: complement and coagulation cascades access
(KEGG；), Reactome muscle contraction access and cardiac conduction access (Reactome),
Gastric cancer access (WikiPathways), and cell cycle/proliferation access, immune
Surveillance/response access and DNA damage/repair access are KEGG, Reactome and WikiPathways
It is jointly comprised.Proliferation access is that tumour is formed and most important access in cell cycle, proliferation related pathways
One of, to the gene expression analysis of Hallmark-50G2/M pathway, 19-GCS risk score and normal tissue, tumor group
Low-risk, high risk composition are knitted with correlation, from normal tissue to tumour low-risk to high risk group, Cyclin D (G1/S
The checkpoint of phase) expression be gradually reduced, the expression of CyclinesE/A/B (promote cell convert to S phase and G2/M phase)
It gradually increases, 19-GCS scoring and the expression of proliferative index Ki-67 and PCNA in clinical application are positively correlated.Immune-mediated is swollen
Cytotoxic effect usually passes through antigen presentation and subsequent CD4+ helper T lymphocyte and CD8+ cytotoxic T cell, and these are specific
Immunocyte come guide infiltration.The antigen that CD4+T cell is presented by detection major histocompatibility complex (MHC) II class
And be activated, and CD8+T cell active cell after detecting the antigen that MHC I class is presented destroys.As 19-GCS risk is commented
The increase divided, the expression of MHC subunit gene gradually decreases, and the expression in high-risk tumour is caused almost to lack.Together
Normal tissue, low danger tumour are compared, and in high-risk tumour, antigen presentation is obviously lacked.Compared with normal tissue, low danger tumour,
In high-risk tumour, the expression including T cell, CD8+T cell and other kinds of tumor infiltrating immunocyte is significantly reduced.Exempt from
Epidemic disease correlation and cell proliferation related because of analysis, path analysis prompt, 19-GCS high risk group accelerates cell Proliferation, promotes
Immunologic escape.
PD: progression of disease (progressive disease), the sum of target lesion maximum diameter at least increases >=20%, or goes out
Now new lesion.SD: stable disease (stable disease), the sum of target lesion maximum diameter reduces and does not reach PR, or increases and do not reach PD.
PR: (partial response) is alleviated in part, and the sum of target lesion maximum diameter reduces >=30%, at least maintains 4 weeks.CR: completely
Alleviate (complete response), all target lesion disappear, and no new lesion occurs, and tumor markers are normal, at least maintain
4 weeks.Using 19-GCS score in predicting I phase patients with lung adenocarcinoma for the first time with the curative effect of successive treatment, 19-GCS high risk with for the first time and
SD in successive treatment is related to PD, and the patient of PD is compared with higher, the patient 19- of recurrence of the patient 19-GCS of CR/PR/SD scoring
GCS scoring is higher, and DISTANT METASTASES IN is higher compared with the risk score of local recurrence.The result is shown in Figure 10 is to Figure 13.
Embodiment 2 carries out prognosis to early stage adenocarcinoma of lung based on 19-GCS scoring
95 I phase patients with lung adenocarcinoma (hospital has made a definite diagnosis), are the volunteer of informed consent.
1, the lung's cancerous tissue for taking patients surgery to obtain, postoperative freeze at once save in -80 degree liquid nitrogen.
2, the RNA of tissue is extracted, the abundance (illuminaHiseq of 19 genes involved in Tables 1 and 2 in RNA is detected
Platform carries out the scoring after the original value that high-flux sequence obtains is standardized with software kit with NGS technology).
The abundance of 8 positive regulating genes is added, numerical value A is obtained.The abundance of 11 negative regulator genes is added, is counted
Value B.Numerical value B is subtracted with numerical value A, obtains 19-GCS scoring.
It is scored based on 19-GCS, is used as threshold value for 53.41, is subdivided into high risk group (High- more than or equal to the threshold value
Risk), low-risk group (Low-Risk) is subdivided into less than the threshold value.95 I phase patients with lung adenocarcinoma, 72 are subdivided into low-risk
Group, 23 are subdivided into high risk group.
Postoperative long term follow-up is carried out to each patient.
The ratio statistical result for tumor of newly swelling in postoperative 5 years is shown in Figure 14.In postoperative 1 year, the postoperative generation of high risk group patient
The ratio for tumor of newly swelling is 25.5%, and the ratio of the new tumor of swelling of the postoperative generation of low-risk group patient is 4.6%.It is high in postoperative 2 years
The ratio of the new tumor of swelling of the postoperative generation of risk group patient is 67.0%, and the ratio of the new tumor of swelling of the postoperative generation of low-risk group patient is
23.6%.
The result is shown in Figure 15 that overall survival counts in postoperative 5 years.Postoperative 5 years, the overall survival of high risk group patient was
11.1%, the overall survival of low-risk group patient is 45.0%.
Claims (10)
1. application of the product first in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma；
The product first is the product for detecting 19 specific genes；
19 specific genes be following 19 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene, SERPINB6 gene, FAM162B gene,
PARK2 gene, GPX3 gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene,
SETDB2 gene, SLC5A4 gene, LRP2BP gene.
2. application of the product second in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma；
The product second is the product for detecting the abundance of 19 specific genes in subject lung cancerous tissue；
The subject is early stage patients with lung adenocarcinoma；
19 specific genes be following 19 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene, SERPINB6 gene, FAM162B gene,
PARK2 gene, GPX3 gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene,
SETDB2 gene, SLC5A4 gene, LRP2BP gene.
3. application of the product third in the system that preparation carries out prognosis to early stage patients with lung adenocarcinoma；
The product third is the product for obtaining 19-GCS scoring；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A be by
In Shi Zhe lung cancerous tissue the abundance of 8 positive regulating genes and value, numerical value B be subject lung cancerous tissue in 11 negative regulations
Gene and value；
The subject is early stage patients with lung adenocarcinoma；
8 positive regulating genes be following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene；
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
4. product first described in claim 1 and the carrier for recording method first -1 carry out early stage patients with lung adenocarcinoma in preparation
Application in the system of prognosis；
Method first -1 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is 8 in subject lung cancerous tissue
The abundance of positive regulating gene and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk, low wind
The prognosis of danger is better than high risk；
The subject is early stage patients with lung adenocarcinoma；
8 positive regulating genes be following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene；
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
5. product second as stated in claim 2 and the carrier for recording method second -1 carry out early stage patients with lung adenocarcinoma in preparation
Application in the system of prognosis；
Method second -1 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is 8 in subject lung cancerous tissue
The abundance of positive regulating gene and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk, low wind
The prognosis of danger is better than high risk；
8 positive regulating genes be following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene；
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
6. product third described in claim 3 and record the carrier of judgment criteria -1 preparation to early stage patients with lung adenocarcinoma into
Application in the system of row prognosis；
The judgment criteria -1 are as follows: the subject of 19-GCS scoring ﹤ threshold value is low-risk, 19-GCS scoring >=threshold value subject
Prognosis for high risk, low-risk is better than high risk.
7. product first described in claim 1 and the carrier for recording method first -2 carry out early stage patients with lung adenocarcinoma in preparation
Application in the system of prognosis；
Method first -2 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is 8 in subject lung cancerous tissue
The abundance of positive regulating gene and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk, Gao Feng
The poor prognosis of danger, the prognosis of low-risk are excellent；
The subject is early stage patients with lung adenocarcinoma；
8 positive regulating genes be following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene；
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
8. product second as stated in claim 2 and the carrier for recording method second -2 carry out early stage patients with lung adenocarcinoma in preparation
Application in the system of prognosis；
Method second -2 includes the following steps:
(1) abundance of 19 specific genes described in subject lung cancerous tissue is detected；
(2) 19-GCS scoring is obtained；19-GCS scoring=numerical value A subtracts numerical value B；Numerical value A is 8 in subject lung cancerous tissue
The abundance of positive regulating gene and value, numerical value B be in subject lung cancerous tissue 11 negative regulator genes and value；
(3) subject of 19-GCS scoring ﹤ threshold value is low-risk, and 19-GCS scoring >=threshold value subject is high risk, Gao Feng
The poor prognosis of danger, the prognosis of low-risk are excellent；
8 positive regulating genes be following 8 genes: ST14 gene, RDH14 gene, DARS gene, CTSL2 gene,
C16orf88 gene, ARL6IP1 gene, SLC6A10P gene, MEX3D gene；
11 negative regulator genes are following 11 genes: SERPINB6 gene, FAM162B gene, PARK2 gene, GPX3
Gene, HLA-DQB1 gene, HOXA2 gene, LOC100128288 gene, RPL13AP17 gene, SETDB2 gene, SLC5A4
Gene, LRP2BP gene.
9. product third described in claim 3 and record the carrier of judgment criteria -2 preparation to early stage patients with lung adenocarcinoma into
Application in the system of row prognosis；
The judgment criteria -2 are as follows: the subject of 19-GCS scoring ﹤ threshold value is low-risk, 19-GCS scoring >=threshold value subject
Prognosis for high risk, the poor prognosis of high risk, low-risk is excellent.
10. a kind of system, purposes is to carry out prognosis to early stage patients with lung adenocarcinoma；
The system is system first or system second or system third；
The system first includes product first described in claim 1；
The system second includes product second as stated in claim 2；
The system third includes product third described in claim 3.
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| CN113755595A (en) * | 2021-09-29 | 2021-12-07 | 首都医科大学附属北京朝阳医院 | Application of 10 gene as target in development of product for prognosis of esophageal squamous cell carcinoma patient |
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Cited By (6)
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| CN111394456A (en) * | 2020-03-19 | 2020-07-10 | 中国医学科学院肿瘤医院 | Early lung adenocarcinoma patient prognosis evaluation system and application thereof |
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| CN113436741A (en) * | 2021-07-16 | 2021-09-24 | 四川大学华西医院 | Lung cancer recurrence prediction method based on tissue specific enhancer region DNA methylation |
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| CN113755595A (en) * | 2021-09-29 | 2021-12-07 | 首都医科大学附属北京朝阳医院 | Application of 10 gene as target in development of product for prognosis of esophageal squamous cell carcinoma patient |
| CN113755595B (en) * | 2021-09-29 | 2023-08-08 | 首都医科大学附属北京朝阳医院 | Application of 10 gene as target in developing product for prognosis of esophageal squamous carcinoma patient |
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