目的:探讨粪便中正大麻受体相关作用蛋白l(cannabinoid receptor interacting protein 1,CNRIPl)和α-突触核蛋白(synuclein-alpha,SNCA)基因甲基化状态及其在结直肠癌和癌前病变中的价值.方法:收集60例结直肠癌、30例腺瘤、20例增生性息肉患者及25名健康人群的清晨粪便标本,采用甲基化特异性PCR技术分析CNRIP1和SNCA的甲基化状态.分析其与结直肠癌临床病例特征的关系,并比较两个基因甲基化单独检测或联合检测与粪便隐血(fecal occult blood test,FOBT)的诊断敏感性.结果:结直肠癌患者粪便DNA中CNRIP1和SNCA基因启动子甲基化率分别为73.3%和60.0%,腺瘤患者分别为56.7%和46.7%,增生性息肉患者分别为20.0%和15.0%,正常对照人群分别为8.0%和4.0%,结直肠癌患者和腺瘤患者无显著性差异,但与其他各组存在显著性差异(P<0.05).2个基因甲基化状态与结直肠癌患者的临床病理指标无明显相关性.CNRIP0和SNCA的甲基化诊断结直肠癌的敏感性分别为73.3%和60.0%,联合检测的敏感性为86.7%,明显高于FOBT的33.3%,而联合检测与单独检测无明显差异.结论:粪便中CNRIP0和SNCA基因启动子甲基化水平在结直肠癌和腺瘤患者中明显升高,其联合检测有望成为结直肠癌及其腺瘤等癌前病变筛查的理想非侵入性检测方法.
Objective:To assess the screening value of CNRIP1 and SNCA methylation in colorectal cancer (CRC) and pre-malignant lesions.Methods:Morning stool samples from different subjects consisting of 60 CRC patients,30 adenoma patients,20 hyperplastic polyps,and 25 healthy controls were collected.The methylation status of Cannabinoid receptor interacting protein 1 (CNRIP1) and Synuclein-alpha (SNCA) in stool samples was evaluated by methylation-specific PCR (MRP).Relationship between clinicopathological features and gene methylation were analyzed.The sensitivity of diagnosis of combining two methylation markers was compared with fecal occult blood test (FOBT).Results:The methylation frequencies of CNRIP1 and SNCA were 73.3% and 60.0% in CRC,56.7% and 46.7% in colon adenomas,20.0% and 15.0% in hyperplastic polys,8.0% and 4.0% in healthy controls,respectively.There was no significant difference for methylation frequencies between CRC group and hyperplastic polys group (P > 0.05),but significantly higher than other two groups (P < 0.05).No significant association existed between genes methylation and clinicopathological.features.The diagnostic sensitivity of CNRIP1 and SNCA for CRC was 73.3% and 60.0%,and the sensitivity of combining two methylation markers was 86.7%.All these sensitivity and specificity were higher than that of FOBT (33.3%),but there was no difference between combining two methylation markers and single methylation markers.Conclusion:DNA methylations levels of CNRIP1 and SCNA in stool samples are significant higher in CRC and adenoma,and combination detecting CNRIP1 and SNCA methylation has great performance for screening colorectal cancer and pre-malignant lesions.