Methylation of TFPI2 in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer

Departments of ¹Surgery, ²Oncology, and ³Pathology, Johns Hopkins University, Baltimore, Maryland; ⁴Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; ⁵Oncomethylome Sciences SA, Liege, Belgium; ⁶Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York; ⁷Department of Pathology, University of Regensburg, Regensburg, Germany; ⁸Department of Pathology, GROW-School for Oncology and Developmental Biology, and ⁹Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; and Departments of ¹⁰Pathology and ¹¹Gastroenterology, VU University Medical Center, Amsterdam, the Netherlands

^* To whom correspondence should be addressed. E-mail: nahuja1{at}jhmi.edu.

	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. [Cancer Res 2009;69(11):OF1–9]

Key Words: TFPI2, methylation, colorectal cancer, stool DNA

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