Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050266
Title: Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer
Authors: Lange 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.
Keywords: carcinoembryonic antigen
genomic DNA
tumor marker
adult
aged
article
blood analysis
C9orf50 gene
cancer diagnosis
cancer staging
colonoscopy
colorectal cancer
controlled study
CpG island
diagnostic test accuracy study
DNA methylation
DNA probe
female
gene
genetic marker
genome analysis
human
human tissue
intermethod comparison
major clinical study
male
sensitivity and specificity
THBD M gene
validation process
Adult
Aged
Case-Control Studies
Cell Line, Tumor
Colorectal Neoplasms
CpG Islands
DNA
DNA Methylation
Female
Genetic Markers
Genome, Human
Humans
Male
Middle Aged
Tumor Markers, Biological
Issue Date: 2012
Citation: Lange 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
Abstract: Background: 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.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161703
ISSN: 19326203
DOI: 10.1371/journal.pone.0050266
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