CN111187840B - Biomarker for early breast cancer diagnosis - Google Patents
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- CN111187840B CN111187840B CN202010100992.0A CN202010100992A CN111187840B CN 111187840 B CN111187840 B CN 111187840B CN 202010100992 A CN202010100992 A CN 202010100992A CN 111187840 B CN111187840 B CN 111187840B
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Abstract
The invention discloses a biomarker for diagnosing early breast cancer, which is LINC01929, and the invention discovers that the expression level of LINC01929 in cancer tissues is obviously up-regulated by detecting a tissue sample and a paracancerous tissue of breast cancer in the I-II stage, so that LINC01929 can be applied to diagnosis and treatment of early breast cancer.
Description
Technical Field
The invention belongs to the field of biological medicine, and relates to a biomarker for diagnosing early breast cancer, wherein the biomarker is LINC01929.
Background
Breast cancer (breast cancer) is one of the most common malignant tumors in women, and usually occurs in mammary epithelial tissue. The incidence of breast Cancer is statistically 7-10% of all malignant tumors throughout the body (Darabi, H et al Breast Cancer risk prediction and individualised screening based on common genetic variation and breast density measure. Breast Cancer Res,2012.14 (1): p.R25.). There is a 135 million new increase in breast Cancer worldwide each year, with 42 thousands of deaths increasing 2% each year (Wen, w., et al Prediction of breast Cancer risk based on common genetic variants in women of East Asian processry. Breast Cancer Res,2016.18 (1): p.124.). More than 4 ten thousand women die from the disease every year in China, and although the women are not in the country with high incidence of breast cancer, the growth rate of the women is far higher than that of the women in other countries. Its pathogenesis is more influential, and genetic susceptibility and gene-to-environment interactions are closely related to its occurrence, progression and metastasis (Mavaddat, net al., prediction of breast Cancer risk based on profiling with common genetic variants.j. Nature Cancer Inst,2015.107 (5)). Although various oncogenes and oncogenes have been found through previous studies to improve the diagnosis rate of breast cancer and the therapeutic effect, the problem has not been completely solved. There is therefore a need for a thorough understanding of the molecular mechanisms of tumorigenesis, providing new and effective therapeutic approaches for the treatment of breast cancer patients. Early diagnosis and early treatment of breast cancer are key to reducing the mortality of breast cancer before the pathogenesis of breast cancer is not completely found.
Long non-coding RNAs (lncRNAs) are a class of nucleotide transcripts lacking protein coding functions, comprising 200 to 100000 nucleotides, with highly conserved sequence elements and specific spatial secondary structures, found in the nucleus or cytoplasm (Hajjari, M., A.Khoshnevisan, and YK.shin, molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer.Tumour Biol,2014.35 (11): p.10645-63.). LncRNAs play an important role in the cell regulation processes of epigenetic regulation, alternative splicing, RNA decay, cell differentiation, cell cycle control, cancer cell metastasis and drug resistance (Richtig, g., et al Function and Clinical Implications of Long Non-Coding RNAs in melanoma.int J Mol Sci,2017.18 (4)). With the intensive research of lncRNAs, there is increasing evidence that lncRNAs are involved in various biological processes and disease pathogenesis, especially tumorigenesis, and that in many human tumors, lncRNAs are commonly differentially expressed. So far, lncRNAs have made little progress in tumors, such as HOTAIR and GWS5, which have been identified as oncogenes and cancer suppressors, respectively. However, the number of lncRNAs is quite large, only a few cancer-related lncRNAs have been reported, and studies on lncRNAs in breast cancer remain in the infancy. Thus, new lncRNAs that are critical for the development and progression of breast cancer are still being discovered and explored by researchers.
Disclosure of Invention
In order to make up the defects of the prior art, the invention aims to provide the lncRNA marker related to the breast cancer, which is applied to clinic, so that the early diagnosis and treatment of the breast cancer are realized, the effective intervention is carried out, and the survival rate and the survival quality of patients are improved.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the invention provides an application of LINC01929 in preparing a product for diagnosing early breast cancer.
Further, the product includes reagents for detecting the expression level of LINC01929 in a sample.
Further, the reagents include reagents for detecting the expression level of LINC01929 by reverse transcription PCR, real-time quantitative PCR, in situ hybridization, chip technology.
The invention provides a product for diagnosing breast cancer, which comprises a chip or a kit, wherein the chip or the kit comprises a reagent for detecting the expression level of LINC01929.
Further, the reagent for detecting the expression level of LINC01929 in the chip comprises a probe for specifically recognizing the LINC01929 gene; the reagent for detecting the expression level of LINC01929 in the kit comprises a primer for specifically amplifying the LINC01929 gene or a probe for specifically identifying the LINC01929 gene.
Further, the primer sequence for specifically amplifying LINC01929 gene is shown as SEQ ID NO. 1-2.
In the present invention, the kit further comprises a container, instructions for use, a positive control, a negative control, a buffer, an auxiliary agent or a solvent, and instructions for use with the kit, wherein it is described how to use the kit for detection, and how to use the detection result for determination of tumor development and selection of a treatment regimen.
The invention provides application of LINC01929 in constructing a calculation model for predicting early breast cancer.
As the skilled person knows, the step of associating a marker level with a certain possibility or risk may be implemented and realized in different ways. Preferably, the measured concentrations of the marker and one or more other markers are mathematically combined and the combined values are correlated with the underlying diagnostic problem. The determination of the marker values may be combined by any suitable prior art mathematical method.
Preferably, the mathematical algorithm applied in the marker combination is a logarithmic function. Preferably, the result of applying such a mathematical algorithm or such a logarithmic function is a single value. Such values can be readily correlated with, for example, an individual's risk for breast cancer or with other intentional diagnostic uses that aid in assessing early breast cancer patients, based on underlying diagnostic issues. In a preferred manner, such a logarithmic function is obtained as follows: a) classifying individuals into groups, such as normal individuals, individuals at risk for breast cancer, patients with breast cancer, etc., b) identifying markers that differ significantly between these groups by univariate analysis, c) logistic regression analysis to evaluate the markers for independent differential values that can be used to evaluate these different groups, and d) constructing a logistic function to combine independent differential values. In this type of analysis, the markers are no longer independent, but represent a combination of markers.
The logarithmic function used to correlate marker combinations with disease preferably employs algorithms developed and obtained by applying statistical methods. For example, suitable statistical methods are Discriminant Analysis (DA) (i.e., linear, quadratic, regular DA), kernel method (i.e., SVM), non-parametric method (i.e., k-nearest neighbor classifier), PLS (partial least squares), tree-based method (i.e., logistic regression, CART, random forest method, boosting/bagging method), generalized linear model (i.e., logistic regression), principal component-based method (i.e., SIMCA), generalized superposition model, fuzzy logic-based method, neural network and genetic algorithm-based method. The skilled artisan will not have problems in selecting an appropriate statistical method to evaluate the marker combinations of the present invention and thereby obtain an appropriate mathematical algorithm. In one embodiment, the statistical method used to obtain the mathematical algorithm used in assessing breast cancer is selected from DA (i.e., linear, quadratic, rule-based discriminant analysis), kernel method (i.e., SVM), non-parametric method (i.e., k-nearest neighbor classifier), PLS (partial least squares), tree-based method (i.e., logistic regression, CART, random forest method, boosting method), or generalized linear model (i.e., logistic regression).
The invention provides application of LINC01929 in screening candidate medicines for treating breast cancer.
Further, the screening steps were as follows:
treating a system expressing or containing the LINC01929 gene with a substance to be screened; and
detecting expression of the LINC01929 gene in the system;
wherein, if the substances to be screened can inhibit the expression level of LINC01929 gene, the substances to be screened are proved to be candidate medicaments for treating breast cancer.
The system is selected from: a cellular system, a subcellular system, a solution system, a tissue system, an organ system, or an animal system.
The candidate substances include (but are not limited to): interfering molecules, nucleic acid inhibitors, small molecule compounds, etc. designed for the LINC01929 gene or its upstream or downstream genes.
The invention provides application of LINC01929 in preparing a pharmaceutical composition for treating breast cancer.
Further, the pharmaceutical composition comprises an inhibitor of LINC01929. The inhibitor is selected from the group consisting of: an interfering molecule targeting LINC01929 or a transcript thereof and capable of inhibiting LINC01929 gene expression or gene transcription comprising: shRNA (small hairpin RNA), small interfering RNA (siRNA), dsRNA, microrna, antisense nucleic acid, or constructs capable of expressing or forming the shRNA, small interfering RNA, dsRNA, microrna, antisense nucleic acid.
Further, the inhibitor is an siRNA. In a specific embodiment of the present invention, the sequence of the siRNA is shown as SEQ ID NO. 5-6.
Further, the pharmaceutical composition also includes a pharmaceutically acceptable carrier including, but not limited to, diluents, binders, surfactants, wetting agents, adsorption carriers, lubricants, fillers, disintegrants.
The pharmaceutical compositions of the invention may also be used in combination with other medicaments for the treatment of breast cancer, and other therapeutic compounds may be administered simultaneously with the primary active ingredient, even in the same composition.
In the present invention, "marker," "biomarker," "genetic marker" may be used interchangeably to refer to a molecular indicator having a specific biological property, biochemical characteristic, or aspect that can be used to determine the presence or absence and/or severity of a particular disease or condition.
In the present invention, the gene for transcription of LINC01929 is located in zone 1 of human 18-chromosome 2 and has an ID of 101927229, and LINC01929 in the present invention includes wild type, mutant or a fragment thereof. A representative LINC01929 is shown as NR_110743.1 disclosed in genebank. As will be appreciated by those skilled in the art, bioinformatic analysis of sequencing results will typically result in an alignment of the sequencing results with known genomes, so long as the sequencing fragments can be aligned to the relevant genes and can be considered as expression of the genes.
The present invention can determine the expression level of a gene using any method known in the art. It will be appreciated by those skilled in the art that the means for determining gene expression is not an important aspect of the present invention. The expression level of the biomarker can be detected at the transcriptional level.
Some methods of detecting or quantifying lncRNA levels are known in the art and are all suitable for use in the methods provided herein to measure the level of a biomarker. Exemplary methods include, but are not limited to, northern blots (northern blots), ribonuclease protection assays, and PCR-based methods.
The assay method may vary depending on the type of lncRNA information desired. Exemplary methods include, but are not limited to, northern blots (Northern blotting) and PCR-based methods (e.g., qRT-PCR). The amount of lncRNA in the sample can be accurately quantified by qRT-PCR and other methods.
The invention has the advantages and beneficial effects that:
the invention discovers that the differential expression of LINC01929 is related to the occurrence and the development of breast cancer for the first time, and can judge whether a subject suffers from early breast cancer or not by detecting the expression level of LINC01929.
The invention discloses a method for screening candidate medicines for treating breast cancer, which judges whether a substance to be screened is a candidate medicine for treating breast cancer by detecting whether the substance to be screened can down regulate the expression level of LINC01929.
Drawings
FIG. 1 is a diagram showing the detection of LINC01929 gene expression in breast cancer tissue by QPCR.
FIG. 2 is a graph showing the effect of CCK-8 detection of LINC01929 gene on proliferation of breast cancer cells.
Detailed Description
The invention is further illustrated below in conjunction with specific examples, which are provided solely for the purpose of illustrating the invention and are not meant to limit the scope of the invention.
The experimental methods used in the following examples are conventional methods unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1 screening for Gene markers associated with early Breast cancer
1. Sample collection
30 cases of breast cancer tissue samples at stage I-II and corresponding paracancerous tissue samples are collected, 5 cases are randomly selected for high-throughput sequencing, all cases are not subjected to chemotherapy and radiotherapy before operation, other neoplastic diseases, autoimmune diseases and serious chronic diseases are eliminated, all patients are informed consent, and the consent of the tissue ethics committee is passed.
2. Preparation of RNA samples
Shearing tissue with scissors, adding 1ml Trizol, and shaking on a shaker for 1min; standing at normal temperature for 10min to decompose nucleoprotein completely; then 200 μl of chloroform (chloroform) is added, the tube cover is closed, the tube cover is vigorously vibrated for 15s, and after standing for 10min at normal temperature, the tube cover is centrifuged at 11000rpm for 15min at 4 ℃; transferring the water sample layer into a new centrifuge tube, and adding 500 μl isopropanol; after being mixed reversely, the mixture is kept stand for 10min at normal temperature and then centrifuged for 15min at 11000rpm at 4 ℃; carefully sucking the liquid with a gun, leaving the precipitate at the bottom of the tube, adding 1ml of 75% ethanol, shaking for 5s on a shaker, washing the precipitate once, and centrifuging at 8000rpm for 5min at 4 ℃; the supernatant was then carefully removed, the precipitate dried for 10min, and the precipitate was dissolved in an appropriate amount of water for 10min.
3. Total RNA quantification and purity analysis
The extracted RNA was subjected to agarose gel electrophoresis, the concentration and purity of the extracted RNA were detected by using Nanodrop2000, the integrity of the RNA was detected by agarose gel electrophoresis, and the RIN value was determined by Agilent 2100. The total amount of RNA required for single library establishment is 5 mug, the concentration is more than or equal to 200 ng/. Mu.L, and OD260/280 is between 1.8 and 2.2.
4. Construction of cDNA library
Removing ribosomal RNA in the total RNA using a Ribo-Zero kit of Epicentre; the complete RNA sequence is randomly broken by metal ions, and RNA is randomly broken into small fragments of about 200 bp; construction of the cDNA library was performed using Illumina TruseqTM RNA sample Prep Kit.
5. Sequencing
2X 150bp sequencing was performed using an Illumina X-Ten sequencing platform.
6. High throughput transcriptome sequencing data analysis
Deleting the lncRNA which is not easily detected, performing differential expression analysis on the numbers of reads using DESeq2 in R-3.3.3 tool, differentially expressing lncRNA screening criteria: FDR <0.05, abs (log 2 FC) >2.
7. Results
The results show that the expression level of LINC01929 was significantly up-regulated in early breast cancer tissues compared to paracancerous tissues.
EXAMPLE 2 QPCR sequencing verifies differential expression of the LINC01929 Gene
1. Large sample QPCR validation was performed on LINC01929 using the 30 previously collected tissue samples of stage I-II breast cancer and paracancerous tissue samples.
2. RNA extraction procedure was as in example 1
3、QPCR
1) Reverse transcription reaction
Reverse transcription of lncRNA was performed using the FastQ μant cDNA first strand synthesis kit from Tiangen Inc. (cat# KR 106).
First, the genomic DNA reaction was removed, 5 Xg of DNA B. Mu.ffer 2.0. Mu.l, 1. Mu.g of total RNA, and RNase Free ddH were added to the tube 2 O was added to a total volume of 10. Mu.l, heated in a water bath at 42℃for 3min, and 10 XFast RT B. Mu.ffer 2.0. Mu.l, RT Enzyme Mix 1.0. Mu.l, FQ-RT Primer Mix 2.0. Mu.l, RNase Free ddH were added 2 O5.0. Mu.l, was mixed and added to the test tube and mixed together to give a total of 20. Mu.l, which was heated at 42℃for 15min and 95℃for 3min in a water bath.
2) Primer design
Designing QPCR amplification primers according to the coding sequences of LINC01929 gene and GAPDH gene in Genebank, and selecting common sequences of different transcription product sequences for designing when designing the primers of LINC01929, wherein the specific primer sequences are as follows:
LINC01929 gene:
the forward primer was 5'-TCCTCTCATACCACTAACATC-3' (SEQ ID NO. 1);
the reverse primer was 5'-GCACCAACTTCAAGACAAT-3' (SEQ ID NO. 2).
GAPDH gene:
the forward primer was 5'-AATCCCATCACCATCTTCCAG-3' (SEQ ID NO. 3);
the reverse primer was 5'-GAGCCCCAGCCTTCTCCAT-3' (SEQ ID NO. 4).
3) qPCR amplification assay
Amplification was performed using SuperReal PreMix Plus (SYBR Green) (cat# FP 205).
20 μl of the reaction system was used: 2X SuperReal PreMix Plus. Mu.l, forward and reverse primers (10. Mu.M) 0.6. Mu.l each, 5X ROX Reference Dye △ 2. Mu.l of DNA template, 2. Mu.l of sterile distilled water, 4.8. Mu.l. Each sample is provided with 3 parallel tubes, and all amplification reactions are repeated more than three times to ensure the reliability of the results.
The amplification procedure was: 95℃for 15min, (95℃for 10s,55℃for 30s,72℃for 32 s). Times.40 cycles.
4) Sample realtem PCR detection
After 10-fold dilution of cDNA of each sample, 2. Mu.l of cDNA was used as a template, and the target gene primer and the internal reference gene primer were used for amplification, respectively. At the same time at 60-95 DEG CPerforming melting curve analysis, determining a target band through melting curve analysis and electrophoresis, and 2 -ΔΔCT The method was used for relative quantification.
4. Statistical analysis
Experiments were performed in 3 replicates and all data were expressed as mean ± standard deviation (mean ± SD). Two groups were compared using a two-sided Student's t test, and three or more groups were analyzed by one-way variance analysis. All results were plotted using GraphPad Software software, with P <0.05 defined as statistically significant differences. ROC curve analysis was performed on variable LINC01929 using SPSS to determine diagnostic efficacy, sensitivity and specificity of the gene.
5. Results
The QPCR results are shown in fig. 1, LINC01929 was up-regulated in early breast cancer tissues compared to paracancerous tissues, the differences were statistically significant (P < 0.05); 29 cases of cancer tissue samples with up-regulated expression and 1 case of cancer tissue samples with no significant difference indicate that LINC01929 can be used as a molecular marker for diagnosing and treating breast cancer.
ROC curve analysis shows that LINC01929 can be used as a biomarker for diagnosing breast cancer, the area under the curve is 0.967, and specific values are shown in table 1, so that LINC01929 expression has high sensitivity and specificity for diagnosing breast cancer.
TABLE 1 area under the curve
Test result variable LINC01929
a. Under non-parametric assumption
b. Zero assumption: real area=0.5
Example 3 Effect of LINC01929 on breast cancer cells
1. Cell culture
BT474 cell line, cell in DMEM medium containing 10% fetal bovine serum (Gibco) in 5% co, for culture of luminel B-type breast cancer 2 Culturing was performed in a constant temperature incubator at 37 ℃. Daily observation of cell growthAnd (3) changing liquid every other day, and performing subculture.
2. Transfection
siRNNA against LINC01929 was designed and synthesized by Shanghai Ji code pharmaceutical technologies Co., ltd, and was compared to the general purpose siRNA-NC.
The siRNA-LINC01929 sequence silencing LINC01929 is shown below.
Sense strand 5'-AAUAUGCACCAACUUCAAGAC-3' (SEQ ID NO. 5)
The antisense strand is 5'-CUUGAAGUUGGUGCAUAUUUC-3' (SEQ ID NO. 6)
Lipofectamin from Invitrogen corporation TM 2000 kit, to transfect LINC01929 siRNA to breast cancer BT474 cell in logarithmic phase, preparing cell in incubator planted in 6 hole plate before cell transfection, 24 hr after transfection, changing liquid and culturing the cell in 6 hole plate. The experiments were divided into 3 groups, blank control (BT 474), negative control (siRNA-NC) and experimental (transfected siRNA).
3. QPCR detection of expression level of LINC01929 in cells
Total cellular RNA was extracted using the Trizol method, and then reverse transcription and real-time quantitative PCR detection were performed as in example 1.
4. CCK-8 detection of the Effect of LINC01929 on proliferation of breast cancer cells
Taking siRNA-LINC01929 transfected breast cancer cells as an experimental group, taking siRNA-NC transfected cells as a control group, adding 5000 cells per well, setting 5 compound wells per group, adding 10 μl of CCK-8 detection solution into the cell wells when culturing for 72h, continuously placing the 96 well plates into a cell incubator for incubation for about 4h, detecting absorbance values of the wells at 450nm wavelength by using an enzyme-labeled instrument, recording data, and detecting proliferation of the cells according to the detected OD value.
5. Statistical analysis
All data are expressed in mean ± standard deviation (mean ± SD). Two groups were compared using a two-sided Student's t test, and three or more groups were analyzed by one-way variance analysis. All results were analyzed using GraphPad Software software, with P <0.05 defined as statistically significant differences.
6. Results
The siRNA transfection result shows that, by taking the expression level of the blank LINC01929 as a reference to be 1, compared with the expression level of LINC01929 of the transfected blank (the relative expression level is 1) and the expression level of LINC01929 of the transfected siRNA-NC group (the relative expression level is 0.920+/-0.036), the expression level of LINC01929 of the transfected siRNA-LINC01929 experimental group (the relative expression level is 0.117+/-0.035) is obviously reduced, the difference has statistical significance (the experimental group vs blank, P=0.0005; the experimental group vs siRNA-NC, P=0.0005), and no obvious difference exists between the siRNA-NC group and the blank (P=0.0615)
As shown in FIG. 2, the results of CCK-8 cell proliferation activity are shown that the OD450 (1.420+ -0.087) of the experimental group transfected with siRNA is obviously lower than that of the control group transfected with siRNA-NC (0.856+ -0.0456), which indicates that LINC01929 can influence proliferation activity of breast cancer cells, and the proliferation capacity of the breast cancer cells can be changed by changing the expression level of LINC01929.
The above description of the embodiments is only for the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that several improvements and modifications can be made to the present invention without departing from the principle of the invention, and these improvements and modifications will fall within the scope of the claims of the invention.
Sequence listing
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Claims (8)
1. Use of an agent that detects the expression level of LINC01929 in a sample for the preparation of a product for diagnosing early breast cancer, wherein the expression level of LINC01929 in early breast cancer tissue is significantly up-regulated compared to paracancerous tissue.
2. The use according to claim 1, wherein the reagent comprises a reagent for detecting the expression level of LINC01929 by reverse transcription PCR, real-time quantitative PCR, in situ hybridization, chip technology.
3. The use of claim 1, wherein the product comprises a chip or a kit, wherein the chip or kit comprises reagents for detecting the expression level of LINC01929.
4. The use according to claim 1, wherein the reagent for detecting the expression level of LINC01929 in the chip comprises a probe specifically recognizing LINC01929 gene; the reagent for detecting the expression level of LINC01929 in the kit comprises a primer for specifically amplifying the LINC01929 gene or a probe for specifically identifying the LINC01929 gene.
5. The use according to claim 4, wherein the primer sequence for specifically amplifying LINC01929 gene is shown in SEQ ID NO. 1-2.
Application of LINC01929 in screening candidate medicines for treating breast cancer, wherein the screening steps are as follows:
treating a system expressing or containing the LINC01929 gene with a substance to be screened; and
detecting expression of the LINC01929 gene in the system;
wherein, if the substances to be screened can inhibit the expression level of LINC01929 gene, the substances to be screened are proved to be candidate medicaments for treating breast cancer.
Use of an inhibitor of linc01929 selected from shRNA, siRNA, antisense nucleic acid, or a construct capable of expressing or forming said shRNA, siRNA, antisense nucleic acid, for the preparation of a pharmaceutical composition for the treatment of breast cancer.
8. The use according to claim 7, wherein the inhibitor is an siRNA.
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| CN108034725A (en) * | 2018-01-08 | 2018-05-15 | 北京泱深生物信息技术有限公司 | Applications of the LINC02185 in breast cancer diagnosis and treatment |
| CN108998532A (en) * | 2018-08-31 | 2018-12-14 | 北京泱深生物信息技术有限公司 | A kind of diagnosis and treatment marker of rectal adenocarcinoma |
| CN109628600A (en) * | 2019-02-20 | 2019-04-16 | 赣南医学院第附属医院 | A kind of biomarker for early-stage breast cancer diagnosis |
Non-Patent Citations (1)
| Title |
|---|
| Nusbaum C.等.Homo sapiens chromosome 18, GRCh38.p12 Primary assembly.Genbank登录号NC_000018 region:55105904-55124306.2018,第1-6页. * |
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