人粪便中基因甲基化分析在大肠癌早期筛查中的意义

Human stool vimentin, oncostatin M receptor and tissue factor pathway inhibitor 2 gene methylation analysis for the detection of colorectal neoplasms

目的探讨联合检测粪便中波形蛋白基因、肿瘤抑素受体（OSMR）基因和组织因子途径抑制物2（TFPI2）基因甲基化作为大肠癌早期筛查的可行性和临床意义。方法收集郑州大学第一附属医院2009年5月至2010年8月收治的60例大肠癌患者、17例大肠腺瘤患者及30名健康对照者的粪便标本，采用甲基化特异性PCR方法分析其波形蛋白基因，OSMR基因和TFPI2基因甲基化状态。结果60例大肠癌患者粪便中波形蛋白基因、OSMR基因和TFPI2基因甲基化阳性率分别为53．3％（32／60），68．3％（41／60）和75．0％（45／60）；17例大肠腺瘤患者3种基因甲基化阳性例数分别为5、7和11例；三者联合检测大肠癌和大肠腺瘤的敏感度分别为86．7％（52／60）和76．5％（13／17），特异度为86．7％（26／30）。结论检测粪便中波形蛋白基因、OSMR基因和TFPI2基因甲基化在大肠癌诊断和筛查中有潜在的应用价值。

Objective To explore the feasibility of detecting vimentin, oncostatin M receptor （OMSR） and tissue factor pathway inhibitor 2 （ TFPI2 ） gene methylation status in stool samples as a noninvasive screening tool for colorectal cancer and precancerous lesions. Methods Stool samples were collected from 60 patients with colorectal cancer, 17 patients with adenoma and 30 normal volunteers. And fecal DNA was extracted and vimentin, OMSR and TFPI2 gene methylation status was analyzed by methylation-specific polymerase chain reaction （MSP）. Results The methylated vimentin, OMSR and TFPI2 was detected in 53.3% （32/60）, 68. 3% （41/60） and 75. 0% （45/60） of colorectal cancer, and 5, 7 and 11 cases of coloreetal adenoma respectively. The sensitivities of combined study, using three markers for the detection of colorectal cancer and colorectal adenomas, were 86. 7% （26/30） and 76. 5% （13/17） respectively. And the specificity was 86.7% （52/60）. Conclusion As a feasible epigenetic marker, promoter hypermethylation for vimentin, OMSR and TFPI2 in stool samples is a sensitive, specific and noninvasive alternative for eolorectal cancer screeninz.