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

被引：195

作者：

Gloeckner, Sabine C. ^{[1
,7
]}

Dhir, Mashaal ^{[1
]}

Yi, Joo Mi ^{[2
]}

McGarvey, Kelly E. ^{[2
]}

Van Neste, Leander ^{[4
]}

Louwagie, Joost ^{[5
]}

Chan, Timothy A. ^{[6
]}

Kleeberger, Wolfram ^{[2
,7
]}

de Bruine, Adriaan P. ^{[8
]}

Smits, Kim M. ^{[8
]}

Bakker, Carolina A. J. Khalid-de ^{[9
]}

Jonkers, Daisy M. A. E. ^{[9
]}

Stockbruegger, Reinhold W. ^{[9
]}

Meijer, Gerrit A. ^{[10
]}

Oort, Frank A. ^{[11
]}

Iacobuzio-Donahue, Christine ^{[3
]}

Bierau, Katja ^{[5
]}

Herman, James G. ^{[2
]}

Baylin, Stephen B. ^{[2
]}

Van Engeland, Marion ^{[8
]}

Schuebe, Kornel E. ^{[2
]}

Ahuja, Nita ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA

[2] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[3] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA

[4] Univ Ghent, Fac Biosci Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium

[5] Oncomethylome Sci SA, Liege, Belgium

[6] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA

[7] Univ Regensburg, Dept Pathol, Regensburg, Germany

[8] Maastricht Univ, Med Ctr, Dept Pathol, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands

[9] Maastricht Univ, Med Ctr, Div Gastroenterol & Hepatol, Dept Internal Med, Maastricht, Netherlands

[10] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands

[11] Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol, Amsterdam, Netherlands

来源：

CANCER RESEARCH | 2009年 / 69卷 / 11期

关键词：

FACTOR PATHWAY INHIBITOR-2; FECAL OCCULT BLOOD; CHROMATIN PATTERN; CELL FATE; GENE; HYPERMETHYLATION; MUTATIONS; MARKER; SFRP2; MECHANISM;

D O I：

10.1158/0008-5472.CAN-08-0142

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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):4691-9]

引用

页码：4691 / 4699

页数：9

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