CN113403398B - Esophageal cancer methylation prognosis markers and application thereof - Google Patents
Esophageal cancer methylation prognosis markers and application thereof Download PDFInfo
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/154—Methylation markers
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Abstract
The invention relates to the field of biotechnology, in particular to a group of esophageal cancer methylation prognosis markers and application thereof; in particular, the set of esophageal cancer methylation prognosis markers comprises at least one of the following methylation sites: cg02370667, cg23378365, cg06090867, cg03244277; meanwhile, the invention provides application of the reagent for detecting the methylation prognosis marker in predicting prognosis of patients with esophageal cancer.
Description
Technical Field
The invention relates to the technical field of biology, in particular to a group of esophageal cancer methylation prognosis markers and application thereof.
Background
Esophageal cancer is a common digestive system malignancy worldwide, with mortality residing in the sixth place of malignant tumor mortality, and morbidity residing in the eighth place (Liang et al 2017;Siegel et al, 2016). Esophageal cancer includes both squamous cell carcinoma and adenocarcinoma major tissue subtypes (Rustgi and El-Serag, 2014), with about 80% of cases of esophageal cancer occurring in underdeveloped countries, and 60% of these cases occurring in china (Ferlay et al, 2010). In recent years, esophageal adenocarcinoma (Esophageal adenocarcinoma, EAC) has been distributed mainly in western countries, and its incidence has rapidly increased, whereas esophageal squamous cell carcinoma (Esophageal squamous cell carcinoma, ESCC) has occurred mainly in some countries in east asia and africa (Brown et al, 2008; zeng et al, 2016). Esophageal squamous carcinoma accounts for about 80% of the total cases of esophageal cancer worldwide (Kamangar et al, 2006), occurring mainly in china, where approximately 35 ten thousand people die annually from this malignancy (Wang et al, 2014). As with many other tumors, early diagnosis of esophageal squamous carcinoma provides a significant improvement in patient prognosis. Due to the lack of an effective early diagnosis, most esophageal squamous carcinoma patients are at advanced stages of the disease when they are diagnosed, and even more than half of them have undergone distant metastasis when they are diagnosed, resulting in a five-year survival rate of less than 30% (Besharat et al, 2008;Enzinger and Mayer,2003). The pathogenesis of esophageal squamous carcinoma is not yet fully elucidated, which is a major bottleneck affecting its treatment.
Tumors are very complex pathological processes involving multiple factors, accumulated through multiple stages of changes, involving multiple levels of complex regulation, such as genome changes, epigenetic changes, transcriptome changes, and signal pathway disorders. Previously, several whole genome or exome sequencing studies have comprehensively summarized genome level changes in esophageal squamous carcinoma, while epigenetic studies have shown multiple molecular level changes, such as DNA methylation, histone acetylation, RNA editing, and the like. In addition, epidemiological studies suggest that it may be relevant to certain environmental factors and lifestyles such as tobacco and wine (Islami et al, 2011;Morita et al, 2010; toh et al, 2010, zhang et al, 2012). Epigenetic changes are also highly susceptible to environmental factors, which can be referred to as changes in genetic material, which combine the effects of both environmental and genetic factors. In recent years, epigenetic changes have been increasingly emphasized in the development of malignant tumors, consistent with other tumors, which contain abnormal localized hypermethylated regions and widely hypomethylated regions in the esophageal squamous carcinoma genome, and aberrations in these epigenetic genomes collectively lead to the development and progression of esophageal squamous carcinoma, such as epigenetic silencing of the cancer suppressor gene, superenhancer activation, and RNA editing (Lin et al, 2018).
With the development of detection technology, alterations in DNA methylation in tumors are considered potential targets for the development of effective diagnostic and prognostic biomarkers. Thus, there are a number of studies reported on DNA methylation-based biomarkers, including diagnostic predictions of various tumors, including lung cancer, colorectal cancer, and gastric cancer (Okugawa et al, 2015;Tahara and Arisawa,2015;Walter et al, 2014), and some methylation markers have been commercialized.
Disclosure of Invention
In order to provide more accurate and efficient markers for predicting prognosis of esophageal cancer patients, the inventor collects medical records and samples of 91 patients, and after methylation sequencing analysis is carried out on cancer tissues and beside cancer tissues, a prognosis model is constructed through single-factor cox regression and multi-factor cox regression analysis, and the model is verified by using data of a network database.
In a first aspect, the invention provides a combination of a set of esophageal cancer methylation prognosis markers, said combination comprising 2, 3, 4 of the following methylation sites: cg02370667, cg23378365, cg06090867, cg03244277.
Specifically, cg02370667 is position 84029511 on chromosome 16, where the gene is NECAB2, which belongs to CpG islands in the methylation site classification.
The cg23378365 is position 156696351 on chromosome 5 and the gene at this site is CYFIP2, which belongs to s_shell (2-4 kbp downstream of CpG island) in the methylation site classification.
The cg06090867 is position 20511782 on chromosome 1, where the gene is UBXN10, which belongs to n_shore (0-2 kbp upstream CpG island) in the methylation site classification.
The cg03244277 is position 75310450 on chromosome 4, where the gene is AREG, which belongs to N_Shore (0-2 kbp upstream CpG island) in methylation site classification.
In particular, the cg02370667 has a high degree of methylation in patients, and the prognosis of patients is worse
The cg23378365 has a high degree of methylation in patients and a poorer prognosis in patients
The cg06090867 has a high degree of methylation in patients and a poorer prognosis in patients
The cg03244277 had a high degree of methylation in patients and had a poorer prognosis.
Preferably, the esophageal cancer includes, but is not limited to, esophageal squamous carcinoma, esophageal adenocarcinoma, esophageal lymphoma, esophageal leiomyosarcoma, and metastatic carcinoma of the esophagus.
Preferably, the esophageal cancer is esophageal squamous carcinoma.
Preferably, the combination may also include other methylation sites.
Preferably, the additional sites include sites located on structural genes and/or non-structural genes.
Preferably, the non-structural gene comprises a cis-acting element and/or a trans-acting element.
Preferably, the combination of esophageal cancer methylation prognosis markers may also be used in combination with other esophageal cancer prognosis markers.
Preferably, the prognostic indicator includes objective remission rate (Objective Response Rate, ORR), overall survival rate (Overall survival rate, overall survival, OS), progression-free survival (PFS), time To Progression (TTP), disease-free survival (DFS), failure to treatment time (time to treatment failure, TTF), response Rate (RR), complete Response (CR), partial Response (PR).
Preferably, the indicator of prognosis is Overall survival (Overall survival rate, over all survivinal, OS).
Preferably, the index of prognosis is overall survival within 100 months. Preferably, overall survival rate is less than 60 months. More preferably, overall survival rate within 50 months.
Preferably, the prognosis is an indication of overall survival, which may also be within 1-5 years. Specifically, the 1-5 years are 1 year, 2 years, 3 years, 4 years, 5 years.
In another aspect, the invention provides a kit for predicting prognosis of esophageal cancer, comprising a methylation detection reagent for detecting at least one marker of the foregoing combinations.
Preferably, the methylation detection reagent comprises a reagent used in any one or more of the following methylation detection methods, the methylation detection method comprising: whole Genome Bisulfite Sequencing (WGBS), pyrosequencing (Pyrosequencing), bisulfite sequencing, methylation-Specific polymerase chain reaction (MS-PCR), bisulfite-Specific polymerase chain reaction, methylation-sensitive restriction enzyme-PCR/Southern method, bisulfite-binding restriction enzyme method (Combined Bisulfite Restriction Analysis, COBRA), digital polymerase chain reaction, restriction landmark genome scanning, cpG island microarray, single nucleotide primer extension (snipe), methylation profile analysis (Methylation Profiling), reagents used by one or more of the methods.
Preferably, the kit further comprises reagents for processing the sample.
Preferably, the treatment may comprise a step of extracting DNA, a step of converting cytosine to uracil.
Preferably, the reagent used in the step of converting cytosine to uracil is most commonly a bisulphite reagent.
Preferably, the bisulphite reagent comprises a bisulphite buffer and a protection buffer.
Preferably, the bisulphite is selected from one or more of sodium bisulphite, sodium sulphite, sodium bisulphite, ammonium bisulphite and ammonium sulphite. Bisulfite reagent treated DNA, which converts unmethylated cytosine nucleotides to uracil, while methylated cytosines and other bases remain unchanged, thus distinguishing between methylated and unmethylated cytidines in, for example, cpG dinucleotide sequences.
Preferably, the extraction reagent for extracting DNA may include a lysis buffer, a binding buffer, a washing buffer, and an elution buffer.
Preferably, the lysis buffer comprises a protein denaturing agent, a detergent, a pH buffer and a nuclease inhibitor.
Preferably, the binding buffer comprises a protein denaturing agent and a pH buffering agent.
Preferably, the detergent includes, but is not limited to, tween20, IGEPAL CA-630, triton X-100, NP-40, and SDS.
Preferably, the pH buffer comprises one or more of Tris, boric acid, phosphate, MES and HEPES.
Preferably, the nuclease inhibitor comprises one or more of EDTA, EGTA and DEPC.
Preferably, the sample comprises: blood, esophageal epithelial cells, tissue, urine, saliva, semen, milk, cerebrospinal fluid, tears, sputum, mucous, lymph, cytosol, ascites, amniotic fluid.
Preferably, the blood comprises plasma, serum or whole blood.
Preferably, the sample is tissue.
Preferably, the kit may further comprise instruments and/or reagents required for detection of clinical indicators.
Preferably, the clinical index detection comprises basic assays such as blood routine, liver and kidney function, blood glucose, electrolytes.
In another aspect, the invention provides a methylation detection reagent for detecting at least one methylation prognosis marker in the combination and the application of the kit for predicting the prognosis of the esophageal cancer.
In another aspect the invention provides a method of predicting the prognosis of esophageal cancer, the method comprising the step of detecting the degree of methylation of at least one methylation prognosis marker of the aforementioned combination in a subject.
Preferably, the subject is a patient diagnosed with esophageal cancer, and the method can stratify the subject into high risk/low risk, representing a prognosis of the patient.
The term "subject" as used herein refers to any animal (e.g., mammal), including but not limited to humans, non-human primates, rodents, etc., that will become the recipient of a particular treatment. In general, the terms "subject" and "patient" are used interchangeably herein when referring to a human subject.
Preferably, the subject is a human.
Preferably, the method comprises a qualitative, quantitative, or semi-quantitative method.
Drawings
FIG. 1 is the result of a survival analysis of a model of the invention and each methylation site in a collected patient sample and TCGA dataset, A is the analysis of a collected patient sample using the model of the invention, B is the analysis of a database using the model of the invention, C is the analysis of a collected patient sample using cg02370667, D is the analysis of a collected patient sample using cg23378365, E is the analysis of a collected patient sample using cg06090867, F is the analysis of a collected patient sample using cg03244277.
Fig. 2 is a ROC graph using patient information to validate the model of the present invention.
Fig. 3 is a ROC graph using database information to validate the model of the present invention.
Detailed Description
The present invention is further described in terms of the following examples, which are given by way of illustration only, and not by way of limitation, of the present invention, and any person skilled in the art may make any modifications to the equivalent examples using the teachings disclosed above. Any simple modification or equivalent variation of the following embodiments according to the technical substance of the present invention falls within the scope of the present invention.
Example 1, collecting data and constructing a prognostic model
Study object
During 2010 to 2014, we collected a total of 91 esophageal squamous carcinoma patients from tumor hospitals of the national academy of medical science and tumor hospitals of Zhejiang province. Demographic and clinical data of native place, ethnicity, sex, age of diagnosis, drinking status, smoking status, tumorigenic site, and clinical stage of all subjects were obtained from medical records of each patient. All patients admitted to the study group are informed of the consent, and the ethical examination committee of tumor hospitals of the academy of sciences of Chinese medicine and tumor hospitals of Zhejiang province has approved related studies.
We performed clinical staging of ESCC patients based on the seventh version of AJCC, which defines the smoking and drinking status of the patient according to the following criteria: the people smoking for less than 1 day and lasting for less than 1 year are judged as non-smokers, otherwise, the people smoking for less than 1 year are smokers; and judging that the drinking times are more than or equal to 2 per week and the drinking time is more than or equal to 1 year as drinking, otherwise, judging that the drinking is not drinking. We completed patient survival follow-up by: study object admission record, confirmation information provided by family members and confirmation information provided by relevant departments of the home location of the patient, the last time of follow-up visit of the patient is 2018, 11 months, and the total time is up to 5 years.
The clinical pathological diagnosis report is used as a standard to judge the pathological type of the patient. None of the study patients underwent chemotherapy or radiation treatment prior to surgery. After transesophageal resection, we selected the cancerous and paracancerous tissue (5 cm away from the edge of the tumor site) of each patient for subsequent study. The samples were screened in groups according to a strict procedure, and the subject was finally selected into the basic clinical data distribution of the patients as shown in Table 1.
TABLE 1 distribution of clinical pathological data in esophageal squamous carcinoma patients
* The upper section: 20-25 cm; middle section: 25-30 cm; the following sections: 30-40 cm.
# Tumor TNM staging was assessed according to the seventh version of esophageal carcinoma, AJCC.
Identification of tumor cell content
First, we obtained cancer and paracancerous tissue cryopreserved at-80 ℃ in the group of patients; then, the unfrozen tissue is treated in time by using a freezing embedding agent, and frozen sections are carried out after the embedding agent is fixed; h & E (H & E) staining was then performed according to the laboratory routine procedure and the stained sections were blocked with neutral gum; finally, we selected more than two pathologists to determine the cancer cell content to meet the following two rules: (1) The content of cancer cells in the cancer tissue is more than or equal to 70 percent, and (2) the cancer-side tissue does not contain cancer cells.
Methylation sequencing and analysis
DNA is extracted, and the DNA can be confirmed by the modes of NanoDrop 2000 detection, qubit detection, running electrophoresis and the like, so that the quality requirements of subsequent DNA methylation detection can be met. After sulfite conversion of the DNA samples, methylation sequencing was performed using Illumina 450K methylation chip (Illumina Human Methylation K loadchip).
The Illumina 450K methylation chip contains 485,512 methylation sites, covers 99% of the coding genes, and also contains other genomic positions: (1) 96% CpG islands; (2) sites outside of CpG islands; (3) non-CpG sites present in stem cells; (4) Sites where normal tissue differs from various tumor tissues; (5) a FANTOM 4 promoter; (6) a dnase hypersensitive site; (7) a miRNA promoter region. The accuracy of the 450K chip detection has been independently verified by two research institutions (Bibikova et al, 2011;Sandoval et al, 2011).
Data analysis
Selection of Wilcoxon rank-sum test statistical testing of paired samples for DNA methylation levels in cancer and paracancerous samples identified 35,577 different methylation sites (FDR <0.05,. DELTA.beta.0.2). In order to fully explore the efficacy of DNA methylation markers in esophageal squamous carcinoma prognosis prediction, we constructed a strict statistical procedure for identification of prognostic markers based on the above-described differential methylation sites:
(1) Screening methylation sites significantly associated with patient survival based on single factor cox regression (P < 0.05);
(2) The 4 methylation sites significantly related to patient survival (corrected age, sex, smoking, drinking, TNM stage) (P < 0.05) were further screened based on multifactor cox regression, the details of the screened methylation sites are shown in Table 2 below, the coefficients, P values, risk ratios, confidence interval information are shown in Table 3,
TABLE 2 methylation site information for multifactor cox regression screening
TABLE 3 information on coefficients, P values, risk ratios, confidence intervals
| Markers | coefficients | P_value | HR | Lower limit of 95% CI | Upper limit of 95% CI |
| cg06090867 | 0.56500274 | 0.03749288 | 1.75945261 | 1.03323766 | 2.99609046 |
| cg03244277 | 0.81793722 | 0.00279055 | 2.26582113 | 1.32545928 | 3.87333315 |
| cg23378365 | 0.58735626 | 0.03652733 | 1.79922543 | 1.03749569 | 3.12021745 |
| cg02370667 | 0.78070752 | 0.00526101 | 2.18301624 | 1.26160139 | 3.77738956 |
(3) We prognostic stratification of patients with the sum of the methylation level at each site and the product of the natural logarithm of the respective risk ratio (HR) (specific formula: cg02370667 x 0.7807075+cg23378333 x 0.5873563+cg06090867 x 0.5650027+cg0324277 x 0.8179372) as predictive score;
(4) Prognosis scores were calculated and survival analyzed in our and TCGA datasets (download website: http:// gdac. Broadenstitute. Org/, 450K methylation chip data containing 95 esophageal squamous carcinomas and 14 paracancerous samples in total), the results of the analysis in patient samples are shown in fig. 1A, and the database is shown in fig. 1B.
Moreover, in the collected patient data, survival analysis was performed for each methylation site individually, and the possibility of each methylation site individually as a prognostic marker was explored, with the results of cg02370667 as in fig. 1c, cg23378365 as in fig. 1d, cg06090867 as in fig. 1e, and cg 0344277 as in fig. 1F.
(5) Again, the accuracy of the model of the present invention was verified at 1 year, 3 years, and 5 years; the ROC curve verified by using patient information is shown in fig. 2, and the ROC curve verified by using database information is shown in fig. 3, which illustrates that the model provided by the invention can predict prognosis of esophageal cancer patients.
Claims (8)
1. Use of a methylation detection reagent for detecting a methylation site consisting of cg02370667, cg23378365, cg06090867 and cg03244277 for the manufacture of a product for predicting prognosis of a patient with esophageal squamous carcinoma.
2. The use of claim 1, wherein the cg02370667 has a high degree of methylation in the patient, the cg23378365 has a high degree of methylation in the patient, the cg06090867 has a high degree of methylation in the patient, and the cg03244277 has a high degree of methylation in the patient.
3. The use according to claim 2, wherein the indicator of prognosis is overall survival.
4. The use according to claim 3, wherein the indicator of prognosis is overall survival within 100 months.
5. The use of claim 3, wherein the prognostic indicator is overall survival within 60 months.
6. The use of claim 3, wherein the prognosis is overall survival of 1 year, 3 years, 5 years.
7. The use of claim 1, wherein the methylation detection reagent comprises a reagent used in any one or more of the following methylation detection methods: whole genome bisulfite sequencing, pyrosequencing, bisulfite sequencing, methylation specific polymerase chain reaction, bisulfite specific polymerase chain reaction, methylation sensitive restriction enzyme-PCR/Southern method, bisulfite-binding restriction enzyme method, digital polymerase chain reaction, restriction landmark genome scanning, cpG island microarray, methylation profile analysis, methylation chip detection.
8. The use of claim 1, wherein the reagent further comprises a reagent for treating a sample.
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| CN104745700A (en) * | 2015-03-27 | 2015-07-01 | 南京医科大学 | Esophageal-cancer-related methylated biomarker and application thereof |
| CN106498085A (en) * | 2016-12-27 | 2017-03-15 | 江苏省人民医院 | A kind of kit for predicting that patients with esophageal squamous cell carcinoma of can performing the operation in early days recurs and shifts risk |
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| WO2019035100A2 (en) * | 2017-08-18 | 2019-02-21 | University Of Southern California | Prognostic markers for cancer recurrence |
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| CN106498085A (en) * | 2016-12-27 | 2017-03-15 | 江苏省人民医院 | A kind of kit for predicting that patients with esophageal squamous cell carcinoma of can performing the operation in early days recurs and shifts risk |
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| Michael S Lee, et al.."Association of CpG island methylator phenotype and EREG/AREG methylation and expression in colorectal cancer".《Br J Cancer》.2016,第114卷(第12期),第1353页右栏第1段，第1357页讨论部分. * |
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