Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis

Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and...

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Veröffentlicht in:PloS one 2014-09, Vol.9 (9), p.e107598
Hauptverfasser: Wang, Yi, Qin, Xiuguang, Wu, Jieqing, Qi, Bo, Tao, Yipeng, Wang, Wenju, Liu, Fulei, Li, Hanchen, Zhao, Baosheng
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Qi, Bo
Tao, Yipeng
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Liu, Fulei
Li, Hanchen
Zhao, Baosheng
description Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer. A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively. Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P
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Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer. A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively. Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P&lt;0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P&lt;0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P&lt;0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P&lt;0.00001). The results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0107598</identifier><identifier>PMID: 25229459</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Cancer ; Carcinogenesis ; Carcinogens ; Cell cycle ; Cell Transformation, Neoplastic - genetics ; Core Binding Factor Alpha 3 Subunit - genetics ; Data processing ; Deactivation ; Disease Progression ; DNA Methylation ; Esophageal cancer ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophagus ; Gastric cancer ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic Association Studies ; Humans ; Inactivation ; Lesions ; Lymph nodes ; Medical prognosis ; Medicine and Health Sciences ; Meta-analysis ; Methylation ; Mucosa ; Prognosis ; Promoter Regions, Genetic ; Publication Bias ; Quality ; Runx3 gene ; Runx3 protein ; Squamous cell carcinoma ; Stomach cancer ; Studies ; Surgery ; Survival ; Thoracic surgery ; Transcription factors ; Tumor suppressor genes ; Tumorigenesis</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e107598</ispartof><rights>2014 Wang et al. 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Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer. A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively. Final analysis of 558 patients from 9 eligible studies was performed. 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RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.</description><subject>Adenocarcinoma</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Cell cycle</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Core Binding Factor Alpha 3 Subunit - genetics</subject><subject>Data processing</subject><subject>Deactivation</subject><subject>Disease Progression</subject><subject>DNA Methylation</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - mortality</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophagus</subject><subject>Gastric cancer</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Lesions</subject><subject>Lymph nodes</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Meta-analysis</subject><subject>Methylation</subject><subject>Mucosa</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Publication Bias</subject><subject>Quality</subject><subject>Runx3 gene</subject><subject>Runx3 protein</subject><subject>Squamous cell carcinoma</subject><subject>Stomach cancer</subject><subject>Studies</subject><subject>Surgery</subject><subject>Survival</subject><subject>Thoracic surgery</subject><subject>Transcription factors</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenesis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNp1kl1rFDEUhoMotlb_gWjA613zPYkXQil-FIqCWPAuZDJndmbJTMYkW9l_76w7XdoLrxJO3vOcN4cXodeUrCmv6Ptt3KXRhfUUR1gTSipp9BN0Tg1nK8UIf_rgfoZe5LwlRHKt1HN0xiRjRkhzjsJlztH3rvRxxLHFU4pDLJDwAKXbh1P9x-23XxxvYAT8py8dLh3gBu4gxGmAsRwkkOPUuQ24gL0bPaQP2B0wDrvZ5z73-SV61rqQ4dVyXqDbz59-Xn1d3Xz_cn11ebPyQqqyUg2ldau40A3nmpvWUMMYacAppnUjhTCStUwZXuv517USzBFfM1k5JWRF-AV6e-ROIWa7LCpbKhVTkldazIrro6KJbmun1A8u7W10vf1XiGljXSq9D2ANJxKop0bMjppa1lx5XnlDHGjCiZpZH5dpu3qAxs_rSC48gj5-GfvObuKdFVRVxugZ8G4BpPh7B7n8x7I4qnyKOSdoTxMosYdE3HfZQyLskoi57c1Dd6em-wjwv7m8s-U</recordid><startdate>20140917</startdate><enddate>20140917</enddate><creator>Wang, Yi</creator><creator>Qin, Xiuguang</creator><creator>Wu, Jieqing</creator><creator>Qi, Bo</creator><creator>Tao, Yipeng</creator><creator>Wang, Wenju</creator><creator>Liu, Fulei</creator><creator>Li, Hanchen</creator><creator>Zhao, Baosheng</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140917</creationdate><title>Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis</title><author>Wang, Yi ; 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Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer. A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively. Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P&lt;0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P&lt;0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P&lt;0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P&lt;0.00001). The results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25229459</pmid><doi>10.1371/journal.pone.0107598</doi><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma
Cancer
Carcinogenesis
Carcinogens
Cell cycle
Cell Transformation, Neoplastic - genetics
Core Binding Factor Alpha 3 Subunit - genetics
Data processing
Deactivation
Disease Progression
DNA Methylation
Esophageal cancer
Esophageal Neoplasms - genetics
Esophageal Neoplasms - mortality
Esophageal Neoplasms - pathology
Esophagus
Gastric cancer
Gene Expression Regulation, Neoplastic
Genes
Genetic Association Studies
Humans
Inactivation
Lesions
Lymph nodes
Medical prognosis
Medicine and Health Sciences
Meta-analysis
Methylation
Mucosa
Prognosis
Promoter Regions, Genetic
Publication Bias
Quality
Runx3 gene
Runx3 protein
Squamous cell carcinoma
Stomach cancer
Studies
Surgery
Survival
Thoracic surgery
Transcription factors
Tumor suppressor genes
Tumorigenesis
title Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis
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