粪便SPG20、FBN1及VIM基因启动子甲基化联合检测在结直肠癌诊断中的意义

Detection of hypermethylated SPG20,FBN1 and VIM in stool samples of patients with colorectal cancer

目的:探讨粪便标本的痉挛性截瘫-20(SPG20)、微纤维蛋白-1(FBN1)及波形蛋白(VIM)基因启动子甲基化联合检测在结直肠癌诊断及筛查中的意义。方法:选取结直肠癌患者75例为观察组,30例健康、年龄匹配的经结肠镜检查阴性者为正常对照组。提取组织及粪便标本DNA,应用甲基化特异性聚合酶链式反应(MSP)方法检测组织及粪便标本中SPG20、FBN1及VIM基因启动子甲基化状态。结果:结直肠癌患者癌组织中SPG20、FBN1及VIM基因启动子甲基化显著高于远癌组织;结直肠癌患者粪便中SPG20、FBN1及VIM基因启动子甲基化显著高于健康对照人群。联合检测显示,96%的患者表现为至少有一个基因启动子区呈现异常的甲基化状态,而在健康人群中,仅有4个(13.3%)呈现基因的异常甲基化状态。因此应用SPG20、FBN1、VIM三个基因启动子区甲基化状态对结直肠癌患者进行筛查的敏感性为96.0%,特异性为86.7%。结论:粪便标本的SPG20、FBN1及VIM基因启动子甲基化联合检测在结直肠癌的诊断和筛查中具有重要的应用价值。

Objective： To clarify the feasibility and clinical significance of detection of SPG20, FBN1 and VIM gene promoter hypermethylation in stool samples of patients with colorectal cancer.Methods： Samples were collected from 75 patients with colorectal cancer and 30 healthy individuals in the first affiliate hospital of Xi＇an Jiaotong University.The methylation status of SPG20, FBN1 and VIM gene promoter in tissue and stool samples was detected using methylation-specific PCR.Results： The methylation rates of SPG20, FBN1 and VIM gene promoter in cancer tissue samples were significantly higher than the distal tissue samples in patients with colorectal cancer.Also, the methylation rates of SPG20, FBN1 and VIM gene promoter in stool samples of patients with colorectal cancer were significantly higher than the healthy individuals.The sensitivity and specificity of combined detection of SPG20, FBN1 and VIM gene promoter methylation status in stool samples in detecting colorectal cancer were 96.0% and 86.7%, respectively.Conclusions： Multi-targets detection of SPG20, FBN1 and VIM gene promoter methylation status in stool samples is a promising approach in the screening of colorectal cancer.