Methylation of TFPI2 in stool DNA: A potential novel biomarker for the detection of colorectal cancer

Sabine C. Glöckner, Mashaal Dhir, Mi Yi Joo, Kelly E. McGarvey, Leander Van Neste, Joost Louwagie, Timothy A. Chan, Wolfram Kleeberger, Adriaan P. De Bruïne, Kim M. Smits, Carolina A.J. Khalid-de Bakker, Daisy M.A.E. Jonkers, Reinhold W. Stockbrügger, Gerrit A. Meijer, Frank A. Oort, Christine Iacobuzio-Donahue, Katja Bierau, James G. Herman, Stephen B. Baylin, Manon Van EngelandKornel E. Schuebel, Nita Ahuja

Research output: Contribution to journalArticlepeer-review

Abstract

We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.

Original languageEnglish (US)
Pages (from-to)4691-4699
Number of pages9
JournalCancer Research
Volume69
Issue number11
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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