粪便SEPT-9和miRNA-34b/c基因甲基化检测在大肠肿瘤筛查中的临床应用

目的 评估检测大肠肿瘤患者粪便中SEPT-9和微RNA（miRNA）-34b/c基因甲基化对大肠肿瘤筛查的临床性能。方法 采用病例对照研究方法,使用甲基化敏感性高分辨率熔解曲线法检测大肠肿瘤患者（大肠癌组35例、大肠腺瘤组47例）和正常对照人群（正常对照组52名）粪便中SEPT-9和miRNA-34b/c基因是否存在甲基化,来评估其筛查大肠肿瘤的性能。结果 大肠癌组SEPT-9和miRNA-34b/c基因的甲基化阳性率分别为68.6%、71.4%,大肠腺瘤组分别为57.4%、63.8%,正常对照组分别为9.6%、11.5%。3组的SEPT-9、miRNA-34b/c基因甲基化阳性率比较差异均有统计学意义（²_SEPT-9 = 37.185,²_miRNA-34b/c = 40.040,P均< 0.001）,利用Bonferroni法进行两两比较,大肠癌组和大肠腺瘤组的甲基化阳性率比较差异无统计学意义,两者与正常对照组比较差异均有统计学意义（P均< 0.001）。3组联合检测SEPT-9和miRNA-34b/c基因的甲基化阳性率为88.6%、76.6%、13.5%,大肠癌组和大肠腺瘤组联合检测的甲基化阳性率均高于SEPT-9单基因检测和miRNA-34b/c单基因检测（P均< 0.05）。结论 检测粪便中SEPT-9和miRNA-34b/c基因甲基化具有效好的大肠肿瘤筛查性能,或许可作为大规模人群筛查大肠肿瘤新的生物标志物组合;多基因甲基化联合检测筛查的性能优于单基因。

Clinical performance of detecting fecal SEPT-9 and miRNA-34b/c gene methylation for colorectal tumor screening

Objective To access the clinical performance of detecting fecal SEPT-9 and miRNA-34b/c gene methylation for colorectal tumor screening in patients diagnosed with colorectal tumor. Methods In this case-control study, the fecal SEPT-9 and miRNA-34b/c gene methylation in patients diagnosed with colorectal cancer（n = 35）,colorectal adenoma（n = 47） and normal controls （n = 52） was identified by by using methylation-sensitive high-resolution melting （MS-HRM） to access the clinical performance for colorectal tumor screening. Results The methylation rates of fecal SEPT-9 and miRNA-34b/c detection in the colorectal cancer group were 68.6% and 71.4%, 57.4% and 63.8% in the colorectal adenoma group, and 9.6% and 11.5% in normal control group, respectively. The methylation rates of SEPT-9 and miRNA-34b/c significantly differed among three groups （²_SEPT-9 = 37.185, ²_miRNA-34b/c = 40.040, all P < 0.001）. According to two-group comparison by using Bonferroni correction,the methylation rates did not significantly differ between the colorectal cancer and colorectal adenoma groups （both P > 0.05）, which significantly differed from those in the normal control group （all P < 0.001）. The methylation rates of combined detection of SEPT-9 and miRNA-34b/c were 88.6% in the colorectal cancer group, 76.6% in the colorectal adenoma group and 13.5% in normal control group. Combined decection methylation rates of SEPT-9 and miRNA-34b in colorectal cancer group and colorectal adenoma group were significantly higher compared with that of either SEPT-9 or miRNA-34b/c alone （all P < 0.05）. Conclusions Detecting fecal SEPT-9 and miRNA-34b/c gene methylation yields high clinical performance for colorectal tumor screening. Methylated SEPT-9 and miRNA-34b/c genes may be a new panel of biomarkers for colorectal tumor screening in large-scale population. The performance of combined detection of multi-gene methylation detection is better compared with that of single gene.