Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050266
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dc.titleGenome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer
dc.contributor.authorLange C.P.E.
dc.contributor.authorCampan M.
dc.contributor.authorHinoue T.
dc.contributor.authorSchmitz R.F.
dc.contributor.authorvan der Meulen-de Jong A.E.
dc.contributor.authorSlingerland H.
dc.contributor.authorKok P.J.M.J.
dc.contributor.authorvan Dijk C.M.
dc.contributor.authorWeisenberger D.J.
dc.contributor.authorShen H.
dc.contributor.authorTollenaar R.A.E.M.
dc.contributor.authorLaird P.W.
dc.date.accessioned2019-11-07T01:15:29Z
dc.date.available2019-11-07T01:15:29Z
dc.date.issued2012
dc.identifier.citationLange C.P.E., Campan M., Hinoue T., Schmitz R.F., van der Meulen-de Jong A.E., Slingerland H., Kok P.J.M.J., van Dijk C.M., Weisenberger D.J., Shen H., Tollenaar R.A.E.M., Laird P.W. (2012). Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer. PLoS ONE 7 (11) : e50266. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0050266
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161703
dc.description.abstractBackground: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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. © 2012 Lange et al.
dc.sourceUnpaywall 20191101
dc.subjectcarcinoembryonic antigen
dc.subjectgenomic DNA
dc.subjecttumor marker
dc.subjectadult
dc.subjectaged
dc.subjectarticle
dc.subjectblood analysis
dc.subjectC9orf50 gene
dc.subjectcancer diagnosis
dc.subjectcancer staging
dc.subjectcolonoscopy
dc.subjectcolorectal cancer
dc.subjectcontrolled study
dc.subjectCpG island
dc.subjectdiagnostic test accuracy study
dc.subjectDNA methylation
dc.subjectDNA probe
dc.subjectfemale
dc.subjectgene
dc.subjectgenetic marker
dc.subjectgenome analysis
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectintermethod comparison
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectsensitivity and specificity
dc.subjectTHBD M gene
dc.subjectvalidation process
dc.subjectAdult
dc.subjectAged
dc.subjectCase-Control Studies
dc.subjectCell Line, Tumor
dc.subjectColorectal Neoplasms
dc.subjectCpG Islands
dc.subjectDNA
dc.subjectDNA Methylation
dc.subjectFemale
dc.subjectGenetic Markers
dc.subjectGenome, Human
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectTumor Markers, Biological
dc.typeArticle
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.doi10.1371/journal.pone.0050266
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue11
dc.description.pagee50266
dc.published.statePublished
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