Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer.
Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer.
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DOI：
10.1158/0008-5472.can-08-0142
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发表时间：
2009-06-01
期刊：
影响因子：
11.2
通讯作者：
Ahuja N
中科院分区：
文献类型：
--
作者：
Glöckner SC;Dhir M;Yi JM;McGarvey KE;Van Neste L;Louwagie J;Chan TA;Kleeberger W;de Bruïne AP;Smits KM;Khalid-de Bakker CA;Jonkers DM;Stockbrügger RW;Meijer GA;Oort FA;Iacobuzio-Donahue C;Bierau K;Herman JG;Baylin SB;Van Engeland M;Schuebel KE;Ahuja N
我们使用基于基因表达阵列的策略来确定组织因子途径抑制物2(TFPI2)的甲基化，这是一种潜在的肿瘤抑制基因，是人类结直肠癌(CRC)中的常见事件。TFPI2属于最近报道的胚胎细胞聚梳组(PcG)标记的基因，在结直肠癌发生的早期阶段可能容易发生异常的DNA甲基化。几乎所有的结直肠癌(97%，n=56)和I~IV期结直肠癌(99%，n=115)都检测到TFPI2的异常甲基化。我们进一步探索了TFPI2作为生物标记物的潜力，在筛选候选对象的非转移性结直肠癌患者和中等风险的非癌症对照组中，使用基于粪便DNA的检测来早期发现结直肠癌。在I~III期大肠癌患者粪便DNA中检测到TFPI2甲基化，其敏感性为76%~89%，特异性为79%~93%。粪便DNA中TFPI2甲基化的检测可能作为未来筛查大肠癌的无创性策略的有用的辅助手段。
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.