粪便中正大麻受体相关作用蛋白1和α-突触核蛋白基因甲基化联合检测在结直肠癌诊断中应用价值

Application value of combined detection of methylation of thepositive cannabinoid receptor associated protein-1 and alpha-synaptic protein gene in the diagnosis of colorectal cancer

[目的]探讨粪便中正大麻受体相关作用蛋白1和α-突触核蛋白基因甲基化联合检测在结直肠癌诊断中应用价值。[方法]收集我院2014年5月~2016年5月收治的结直肠癌患者、癌前病变患者以及健康志愿者各50例的清晨粪便标本,分别作为结直肠癌组、癌前病变组和健康对照组,做好标记后,应用巢式甲基化特异性PCR(nested methylation specific PCR,nMSP)技术对3组正大麻受体相关作用蛋白1(cannabinoid receptor interacting protein 1,CNRIPl)和α-突触核蛋白(synuclein-alpha,SNCA)基因甲基化状态进行检测、比较,并对比此种诊断方案和粪便隐血(feces occult blood test,FOBT)对结直肠癌组诊断的灵敏度和特异度、诊断准确度。[结果](1)结直肠癌组DNA的CNRIPl和SNCA基因启动子甲基化率分别为74.0%和60.0%,癌前病变组分别为50.0%和40.0%,正常对照组分别为8.0%和4.0%,3组间两两比较,差异均有统计学意义(P<0.05)。(2)经病理检查确诊的结直肠癌组50患者中,经粪便中CNRIPl和SNCA基因甲基化联合检测确诊43例,灵敏度及诊断准确度均为86.0%,特异度为0;经FOBT确诊16例,灵敏度及诊断准确度均为32.0%,特异度为0。2种检查手段在直肠癌诊断中的灵敏度及诊断准确度比较,差异有统计学意义(P<0.05)。[结论]粪便中CNRIPl和SNCA基因甲基化联合检测在结直肠癌诊断中具有较高的灵敏度和准确度,可作为结直肠癌及癌前病变筛查的理想方法,安全无创,应用价值高。

[Objective]To explore the application value of combined detection of the methylation of the positive cannabinoid receptor associated protein-1and alpha-synaptic protein gene in the diagnosis of colorectal cancer.[Methods]From May 2014 to May 2016,the early morning stool specimens colorectal of cancer patients,precancerous lesion patients and 50 healthy volunteers in our hospital were enrolled,respectively as colorectal cancer group,precancerous lesion group and healthy control group.After marking,the nested methylation specific PCR（nMSP）technology was used to detect and compare the methylation status of cannabinoid receptor interacting protein-1（CNRIP-l）and alpha-synuclein（SNCA）gene in the three groups.While compared this diagnosis and fecal occult blood（FOBT）on the diagnosis of colorectal cancer sensitivity,specificity and diagnostic accuracy.[Results]The promoter methylation rates of CNRIP1 and SNCA genes in colorectal cancer group were 74.0%and 60.0%respectively,50.0%and 40.0%in the precancerous lesion group,8.0% and 4%in the normal control group,three groups were compared between two,the differences were statistically significant（P0.05）.Pathological examination of colorectal cancergroup diagnosed in 50 patients,the fecal CNRIPl and SNCA gene methylation combined detection of 43 cases,the sensitivity and diagnostic accuracy were 86.0%,specificity of 0%;16cases with FOBT diagnosed,the sensitivity and accuracy of diagnosis was 32%,the specificity was 0%.The sensitivity and diagnostic accuracy of the two methods in the diagnosis of rectal cancer were compared,and the differences were statistically significant（P0.05）.[Conclusion]The combined detection of CNRIPl and SNCA gene methylation in feces has high sensitivity and accuracy in the diagnosis of colorectal cancer,and can be used as an ideal method of screenin for colorectal cancer and precancerous lesions,with safe,noninvasive and high application value.