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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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 |
doi_str_mv | 10.1371/journal.pone.0107598 |
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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<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<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<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<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. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Wang et al 2014 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-6d11bf6348d33839f919220dea6288d544952f2693b8759b642a0cb257a645703</citedby><cites>FETCH-LOGICAL-c456t-6d11bf6348d33839f919220dea6288d544952f2693b8759b642a0cb257a645703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167998/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167998/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25229459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wei, Qing-Yi</contributor><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Qin, Xiuguang</creatorcontrib><creatorcontrib>Wu, Jieqing</creatorcontrib><creatorcontrib>Qi, Bo</creatorcontrib><creatorcontrib>Tao, Yipeng</creatorcontrib><creatorcontrib>Wang, Wenju</creatorcontrib><creatorcontrib>Liu, Fulei</creatorcontrib><creatorcontrib>Li, Hanchen</creatorcontrib><creatorcontrib>Zhao, Baosheng</creatorcontrib><title>Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><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<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<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<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<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><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 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of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis</title><author>Wang, Yi ; Qin, Xiuguang ; Wu, Jieqing ; Qi, Bo ; Tao, Yipeng ; Wang, Wenju ; Liu, Fulei ; Li, Hanchen ; Zhao, Baosheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-6d11bf6348d33839f919220dea6288d544952f2693b8759b642a0cb257a645703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenocarcinoma</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Cell cycle</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Core Binding Factor Alpha 3 Subunit - genetics</topic><topic>Data processing</topic><topic>Deactivation</topic><topic>Disease Progression</topic><topic>DNA Methylation</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - mortality</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophagus</topic><topic>Gastric cancer</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic Association Studies</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Lesions</topic><topic>Lymph nodes</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Meta-analysis</topic><topic>Methylation</topic><topic>Mucosa</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Publication Bias</topic><topic>Quality</topic><topic>Runx3 gene</topic><topic>Runx3 protein</topic><topic>Squamous cell carcinoma</topic><topic>Stomach cancer</topic><topic>Studies</topic><topic>Surgery</topic><topic>Survival</topic><topic>Thoracic surgery</topic><topic>Transcription factors</topic><topic>Tumor suppressor 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yi</au><au>Qin, Xiuguang</au><au>Wu, Jieqing</au><au>Qi, Bo</au><au>Tao, Yipeng</au><au>Wang, Wenju</au><au>Liu, Fulei</au><au>Li, Hanchen</au><au>Zhao, Baosheng</au><au>Wei, Qing-Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-17</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e107598</spage><pages>e107598-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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<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<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<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<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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