检测粪便中SFRP2基因超甲基化对筛查结直肠癌的意义

Hypermethylated SFRP2 gene in fecal DNA is a high potential molecular marker for colorectal cancer screening

目的探讨粪便中分泌型卷曲相关蛋白2(SFRP2)基因超甲基化作为筛查大肠癌的非侵袭性方法的可行性。方法用甲基化荧光定量PCR(Methylight)技术分析大肠癌69例,腺瘤34例和增生性息肉26例瘤组织和粪便中SFRP2基因甲基化状态,30例健康者作为对照。同时,分析SFRP2基因甲基化与肿瘤临床病理特点之间的关系。结果SFRP2基因在91.3%(63/69)的大肠癌组织、79.4%(27/34)的进展型腺瘤组织和53.8%(14/26)的增生性息肉组织中发生超甲基化,在同一患者所对应的粪便中有87.0%(60/69)、61.8%(21/34)和42.3%(11/26)发生超甲基化。在正常对照的结肠黏膜组织中没有检测到SFRP2基因甲基化,但在粪便中有2例发生了SFRP2基因超甲基化。此外,SFRP2超甲基化与肿瘤的临床特征包括性别、年龄、肿瘤分期、位置及病理分级等无显著相关性。结论粪便中SFRP2基因超甲基化是大肠癌的一种新的分子标记物,对于非侵袭性检测大肠癌具有高度的潜力。

Objective To investigate the feasibility of detecting hypermethylated secreted frizzled - related protein 2 （SFRtr2） gene in fecal DNA as a non - invasive screening tool for colorectal cancer （ CRC ）. Methods Fluorescence - based real - time PCR assay （MethyLight） was performed to analyze SFRP2 gene promoter metbylation status in a blinded fashion in tumor tissues and in stool samples taken from 69 CRC patients preoperatively, 34 patients with adenoma ≥ 1 cm, 26 with hyperplastic polyp, and 30 endoscopically normal subjects. Simultaneously the relationship between hypermethylation of SFRP2 gene and clinicopathological features was analyzed. Results SFRP2 gene was hypermethylated in91.3% （63/69） of CRC, 79.4% （27/34） of adenoma and53.8% （14/26） of hyperplastic polyp tissues, and in 87.0% （60/69）, 61.8% （21/34） and 42.3 % （ 11/26 ） of corresponding fecal samples, respectively. In contrast, no methylated SFRP2 gene was detected in mucosal tissues of normal controls, while two cases of matched fecal samples from normal controls with hypermethylated SFRP2 were detected. Moreover, no significant associations were observed between SFRP2 hypermethylation and clinicopathological features including sex, age, tumor stage, site, lymph node status and histological grade. Conclusion Hypennethylation of SFRP2 gene in fecal DNA is a novel molecular biomarker of CRC and affords a high potential for the remote detection of CRC and premalignant lesions as a noninvasive screening method.