Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer
Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tis...
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| Veröffentlicht in: | Journal of investigative medicine 2016-10, Vol.64 (7), p.1200-1207 |
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| creator | Chang, Hsien-Feng Wu, Chang-Chieh Sun, Chien-An Chu, Chi-Ming Lin, Fu-Gong Hsieh, Jih-Fu Hsu, Chih-Hsiung Huang, Chi-Hua Yang, Tsan Tsai, Yang-Ming Kuan, Jen-Chun Chou, Yu-Ching |
| description | Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p |
| doi_str_mv | 10.1136/jim-2016-000086 |
| format | Article |
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We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p<0.001). In addition, after stratification by promoter methylation in 3 combined genes in the matched normal tissues, we observed a joint effect after adjusting for sex, age at surgery, and adjuvant chemotherapy, yielding a significant OR of 20.35 (95% CI 4.16 to 99.57; p<0.001). DNA methylation status would significantly increase the recurrence risk of CRC with a significant impact on joint effect between DNA methylation and clinical stage, particularly in matched normal tissues. This was attributed to molecular changes that could not be examined on the basis of clinical pathology. Our interaction results may serve as a reference marker for evaluating the risk of recurrence in future studies.</description><identifier>ISSN: 1081-5589</identifier><identifier>EISSN: 1708-8267</identifier><identifier>DOI: 10.1136/jim-2016-000086</identifier><identifier>PMID: 27296458</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Aged ; Binding sites ; Biomarkers ; Cell cycle ; Clinical medicine ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - surgery ; Cyclin-dependent kinases ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Epigenetics ; Female ; Gene expression ; Humans ; Kinases ; Male ; Medical prognosis ; Medical records ; Metastasis ; Middle Aged ; Mortality ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - mortality ; Neoplasm Staging ; Odds Ratio ; Promoter Regions, Genetic ; Public health ; Risk Factors ; Studies ; Surgery ; Tumors</subject><ispartof>Journal of investigative medicine, 2016-10, Vol.64 (7), p.1200-1207</ispartof><rights>Copyright © 2016 American Federation for Medical Research</rights><rights>2016 American Federation for Medical Research</rights><rights>Copyright © 2016 American Federation for Medical Research.</rights><rights>Copyright © 2016 American Federation for Medical Research2016JIM</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b397t-e175965cfb250157fa8ed48dc3d9e42859b8fc628224010dbd3ec078f21090c63</citedby><cites>FETCH-LOGICAL-b397t-e175965cfb250157fa8ed48dc3d9e42859b8fc628224010dbd3ec078f21090c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1136/jim-2016-000086$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1136/jim-2016-000086$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27296458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Hsien-Feng</creatorcontrib><creatorcontrib>Wu, Chang-Chieh</creatorcontrib><creatorcontrib>Sun, Chien-An</creatorcontrib><creatorcontrib>Chu, Chi-Ming</creatorcontrib><creatorcontrib>Lin, Fu-Gong</creatorcontrib><creatorcontrib>Hsieh, Jih-Fu</creatorcontrib><creatorcontrib>Hsu, Chih-Hsiung</creatorcontrib><creatorcontrib>Huang, Chi-Hua</creatorcontrib><creatorcontrib>Yang, Tsan</creatorcontrib><creatorcontrib>Tsai, Yang-Ming</creatorcontrib><creatorcontrib>Kuan, Jen-Chun</creatorcontrib><creatorcontrib>Chou, Yu-Ching</creatorcontrib><title>Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer</title><title>Journal of investigative medicine</title><addtitle>J Investig Med</addtitle><description>Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p<0.001). In addition, after stratification by promoter methylation in 3 combined genes in the matched normal tissues, we observed a joint effect after adjusting for sex, age at surgery, and adjuvant chemotherapy, yielding a significant OR of 20.35 (95% CI 4.16 to 99.57; p<0.001). DNA methylation status would significantly increase the recurrence risk of CRC with a significant impact on joint effect between DNA methylation and clinical stage, particularly in matched normal tissues. This was attributed to molecular changes that could not be examined on the basis of clinical pathology. Our interaction results may serve as a reference marker for evaluating the risk of recurrence in future studies.</description><subject>Aged</subject><subject>Binding sites</subject><subject>Biomarkers</subject><subject>Cell cycle</subject><subject>Clinical medicine</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Cyclin-dependent kinases</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical records</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Staging</subject><subject>Odds Ratio</subject><subject>Promoter Regions, Genetic</subject><subject>Public health</subject><subject>Risk Factors</subject><subject>Studies</subject><subject>Surgery</subject><subject>Tumors</subject><issn>1081-5589</issn><issn>1708-8267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkM9PwyAYhonRuDk9ezMk3ox1QAul3pb5M1n0oueGUuqobZlAY3bxb5fZqScjF8j7PTxf8gJwjNEFxjGb1rqNCMIsQuFwtgPGOEU84oSlu-GNOI4o5dkIHDhXI0QYzcg-GJGUZCyhfAw-5o3utBQNdF68KCi6ElrtXqGpoFWyt1Z1cohbY71otF9fQt15ZYX02nQb8OphBlvll-tGfEVVGBnrAgZXIVGdd_Bd-yWUpjHBGjRQiuC1h2CvEo1TR9t7Ap5vrp_md9Hi8fZ-PltERZylPlI4pRmjsioIRZimleCqTHgp4zJTCeE0K3glGeGEJAijsihjJVHKK4JRhiSLJ-B08K6seeuV83ltetuFlTmJURqUhCWBmg6UtMY5q6p8ZXUr7DrHKN_0nYe-803f-dB3-HGy9fZFq8of_rvgAJwPgAvt_i7923c24EVb_7v8E1zGl30</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Chang, Hsien-Feng</creator><creator>Wu, Chang-Chieh</creator><creator>Sun, Chien-An</creator><creator>Chu, Chi-Ming</creator><creator>Lin, Fu-Gong</creator><creator>Hsieh, Jih-Fu</creator><creator>Hsu, Chih-Hsiung</creator><creator>Huang, Chi-Hua</creator><creator>Yang, Tsan</creator><creator>Tsai, Yang-Ming</creator><creator>Kuan, Jen-Chun</creator><creator>Chou, Yu-Ching</creator><general>SAGE Publications</general><general>Sage Publications Ltd</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>0-V</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AM</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGRYB</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K7.</scope><scope>K9.</scope><scope>M0O</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>201610</creationdate><title>Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer</title><author>Chang, Hsien-Feng ; Wu, Chang-Chieh ; Sun, Chien-An ; Chu, Chi-Ming ; Lin, Fu-Gong ; Hsieh, Jih-Fu ; Hsu, Chih-Hsiung ; Huang, Chi-Hua ; Yang, Tsan ; Tsai, Yang-Ming ; Kuan, Jen-Chun ; Chou, Yu-Ching</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b397t-e175965cfb250157fa8ed48dc3d9e42859b8fc628224010dbd3ec078f21090c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aged</topic><topic>Binding sites</topic><topic>Biomarkers</topic><topic>Cell cycle</topic><topic>Clinical medicine</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - surgery</topic><topic>Cyclin-dependent kinases</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Kinases</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical records</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Neoplasm Staging</topic><topic>Odds Ratio</topic><topic>Promoter Regions, Genetic</topic><topic>Public health</topic><topic>Risk Factors</topic><topic>Studies</topic><topic>Surgery</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Hsien-Feng</creatorcontrib><creatorcontrib>Wu, Chang-Chieh</creatorcontrib><creatorcontrib>Sun, Chien-An</creatorcontrib><creatorcontrib>Chu, Chi-Ming</creatorcontrib><creatorcontrib>Lin, Fu-Gong</creatorcontrib><creatorcontrib>Hsieh, Jih-Fu</creatorcontrib><creatorcontrib>Hsu, Chih-Hsiung</creatorcontrib><creatorcontrib>Huang, Chi-Hua</creatorcontrib><creatorcontrib>Yang, Tsan</creatorcontrib><creatorcontrib>Tsai, Yang-Ming</creatorcontrib><creatorcontrib>Kuan, Jen-Chun</creatorcontrib><creatorcontrib>Chou, Yu-Ching</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Criminal Justice Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Criminology Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Criminal Justice</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><jtitle>Journal of investigative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Hsien-Feng</au><au>Wu, Chang-Chieh</au><au>Sun, Chien-An</au><au>Chu, Chi-Ming</au><au>Lin, Fu-Gong</au><au>Hsieh, Jih-Fu</au><au>Hsu, Chih-Hsiung</au><au>Huang, Chi-Hua</au><au>Yang, Tsan</au><au>Tsai, Yang-Ming</au><au>Kuan, Jen-Chun</au><au>Chou, Yu-Ching</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer</atitle><jtitle>Journal of investigative medicine</jtitle><addtitle>J Investig Med</addtitle><date>2016-10</date><risdate>2016</risdate><volume>64</volume><issue>7</issue><spage>1200</spage><epage>1207</epage><pages>1200-1207</pages><issn>1081-5589</issn><eissn>1708-8267</eissn><abstract>Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p<0.001). In addition, after stratification by promoter methylation in 3 combined genes in the matched normal tissues, we observed a joint effect after adjusting for sex, age at surgery, and adjuvant chemotherapy, yielding a significant OR of 20.35 (95% CI 4.16 to 99.57; p<0.001). DNA methylation status would significantly increase the recurrence risk of CRC with a significant impact on joint effect between DNA methylation and clinical stage, particularly in matched normal tissues. This was attributed to molecular changes that could not be examined on the basis of clinical pathology. Our interaction results may serve as a reference marker for evaluating the risk of recurrence in future studies.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>27296458</pmid><doi>10.1136/jim-2016-000086</doi><tpages>8</tpages></addata></record> |
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| subjects | Aged Binding sites Biomarkers Cell cycle Clinical medicine Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - mortality Colorectal Neoplasms - surgery Cyclin-dependent kinases Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics Epigenetics Female Gene expression Humans Kinases Male Medical prognosis Medical records Metastasis Middle Aged Mortality Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - mortality Neoplasm Staging Odds Ratio Promoter Regions, Genetic Public health Risk Factors Studies Surgery Tumors |
| title | Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer |
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