摘要
目的:评估粪便中转录因子GATA结合蛋白5(GATA binding protein 5,GATA5)和波形蛋白(Vimentin)基因启动子甲基化标志的检测用于结直肠癌(colorectal cancer,CRC)早期无创诊断的可行性.方法:收集浙江省宁波市医疗中心李惠利医院2012-02/2012-12的49例CRC患者和37例正常对照者的粪便,从中分别提取DNA,并采用甲基化特异性PCR(methylation-specificpolymerase chain reaction,MSP)技术分析GATA5和Vimentin基因启动子的甲基化状态.结果:在CRC患者中,检测GATA5基因甲基化诊断CRC的敏感性和特异性分别为81.63%和86.49%,Vimentin基因甲基化的敏感性和特异性分别为44.90%和86.49%,两个基因中至少有一个基因甲基化的概率为95.1%,相比之下,37个正常样本中只有10个(27.0%)显示有DNA甲基化.单因素相关分析显示,GATA5和Vimentin基因甲基化的阳性状态与CRC患者年龄、性别、肿瘤的分期和位置无统计学相关性.结论:CRC粪便DNA中GATA5和Vimentin基因异常甲基化发生率明显高于正常对照组,粪便样本中检测GATA5和Vimentin基因甲基化可能成为CRC早期无创诊断的一个新方法,并且联合检测多基因甲基化筛查结直肠肿瘤的方法优于单基因检测方法.
AIM: To evaluate the possibility of using GATAbinding protein 5(GATA5) and Vimentin promoter methylation as markers for the noninvasive detection of colorectal cancer(CRC). METHODS: Stool samples were collected from49 patients with CRC and 37 endoscopicallynormal subjects who underwent colonoscopy atour hospital from February 2012 to December2012, and DNA was isolated from all samples.Methylation-specific polymerase chain reaction(MSP) was then utilized to analyze promoter CpG methylation of GATA5 and Vimentin. RESULTS: The sensitivity and specificity of GATA5 gene methylation assay for detection of colorectal cancer were 81.63% and 86.49%, respectively. The sensitivity and specificity of Vimentin gene methylation were 44.90% and 86.49%, respectively. The overall sensitivity of detection of fecal DNA with at least one methylated gene was 95.1% in patients with CRC. In contrast, only 10 of the 37(27.0%) normal individuals exhibited methylated DNA in the above promoter regions. GATA5 and Vimentin promoter methylation showed no significant correlation with gender, age, tumor-node-metastasis(TNM) stage or tumor location. CONCLUSION: The abnormal methylation of GATA5 and Vimentin occurs frequently in fecal samples of patients with colorectal cancer. Detection of aberrantly methylated GATA5 and Vimentin in fecal samples may be a promising, noninvasive screening method for colorectal cancer, and the combined detection of multiple gene methylation for colorectal neoplasia screening is superior to single gene detection.
出处
《世界华人消化杂志》
CAS
北大核心
2014年第20期2971-2976,共6页
World Chinese Journal of Digestology
基金
宁波市社会发展基金资助项目
No.2011C50022~~