Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer
There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-based detection of colorectal cancer. We used DNA methylation data from 7...
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| Veröffentlicht in: | PloS one 2012-11, Vol.7 (11), p.e50266-e50266 |
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| creator | Lange, Christopher P E Campan, Mihaela Hinoue, Toshinori Schmitz, Roderick F van der Meulen-de Jong, Andrea E Slingerland, Hilde Kok, Peter J M J van Dijk, Cornelis M Weisenberger, Daniel J Shen, Hui Tollenaar, Robertus A E M Laird, Peter W |
| description | There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-based detection of colorectal cancer.
We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection.
Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing. |
| doi_str_mv | 10.1371/journal.pone.0050266 |
| format | Article |
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We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection.
Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0050266</identifier><identifier>PMID: 23209692</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Biological markers ; Biology ; Biomarkers ; Biomarkers, Tumor - metabolism ; Blood ; Blood tests ; Breast cancer ; Cancer ; Cancer diagnosis ; Cancer genetics ; Cancer research ; Cancer therapies ; Carcinoembryonic antigen ; Case-Control Studies ; Cell Line, Tumor ; Colon ; Colonoscopy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - blood ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - genetics ; CpG Islands ; Deoxyribonucleic acid ; Disease ; DNA ; DNA - genetics ; DNA Methylation ; Endoscopy ; Epigenetics ; Female ; Gastroenterology ; Gastrointestinal diseases ; Genetic aspects ; Genetic Markers - genetics ; Genome, Human ; Genomes ; Genomics ; Health aspects ; Hepatology ; Hospitals ; Humans ; Inflammatory bowel disease ; Male ; Medical prognosis ; Medical research ; Medicine ; Methylation ; Middle Aged ; Optimization ; Plasma ; Studies ; Surgery ; Surveillance ; Tumors</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e50266-e50266</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Lange et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2012 Lange et al 2012 Lange et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-1f7879ce431a5a906a16c4069b4f3b8e42aeefccc28ca00585234b0d5fd3dc983</citedby><cites>FETCH-LOGICAL-c758t-1f7879ce431a5a906a16c4069b4f3b8e42aeefccc28ca00585234b0d5fd3dc983</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/PMC3508917/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508917/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23209692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lange, Christopher P E</creatorcontrib><creatorcontrib>Campan, Mihaela</creatorcontrib><creatorcontrib>Hinoue, Toshinori</creatorcontrib><creatorcontrib>Schmitz, Roderick F</creatorcontrib><creatorcontrib>van der Meulen-de Jong, Andrea E</creatorcontrib><creatorcontrib>Slingerland, Hilde</creatorcontrib><creatorcontrib>Kok, Peter J M J</creatorcontrib><creatorcontrib>van Dijk, Cornelis M</creatorcontrib><creatorcontrib>Weisenberger, Daniel J</creatorcontrib><creatorcontrib>Shen, Hui</creatorcontrib><creatorcontrib>Tollenaar, Robertus A E M</creatorcontrib><creatorcontrib>Laird, Peter W</creatorcontrib><title>Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-based detection of colorectal cancer.
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Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. 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Hilde</au><au>Kok, Peter J M J</au><au>van Dijk, Cornelis M</au><au>Weisenberger, Daniel J</au><au>Shen, Hui</au><au>Tollenaar, Robertus A E M</au><au>Laird, Peter W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-11-28</date><risdate>2012</risdate><volume>7</volume><issue>11</issue><spage>e50266</spage><epage>e50266</epage><pages>e50266-e50266</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-based detection of colorectal cancer.
We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection.
Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23209692</pmid><doi>10.1371/journal.pone.0050266</doi><tpages>e50266</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1350901218 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Biological markers Biology Biomarkers Biomarkers, Tumor - metabolism Blood Blood tests Breast cancer Cancer Cancer diagnosis Cancer genetics Cancer research Cancer therapies Carcinoembryonic antigen Case-Control Studies Cell Line, Tumor Colon Colonoscopy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - blood Colorectal Neoplasms - diagnosis Colorectal Neoplasms - genetics CpG Islands Deoxyribonucleic acid Disease DNA DNA - genetics DNA Methylation Endoscopy Epigenetics Female Gastroenterology Gastrointestinal diseases Genetic aspects Genetic Markers - genetics Genome, Human Genomes Genomics Health aspects Hepatology Hospitals Humans Inflammatory bowel disease Male Medical prognosis Medical research Medicine Methylation Middle Aged Optimization Plasma Studies Surgery Surveillance Tumors |
| title | Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T14%3A18%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-scale%20discovery%20of%20DNA-methylation%20biomarkers%20for%20blood-based%20detection%20of%20colorectal%20cancer&rft.jtitle=PloS%20one&rft.au=Lange,%20Christopher%20P%20E&rft.date=2012-11-28&rft.volume=7&rft.issue=11&rft.spage=e50266&rft.epage=e50266&rft.pages=e50266-e50266&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0050266&rft_dat=%3Cgale_plos_%3EA477008412%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1350901218&rft_id=info:pmid/23209692&rft_galeid=A477008412&rft_doaj_id=oai_doaj_org_article_fada6eca2e264ae695fc74a84b5c1f63&rfr_iscdi=true |