南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (6): 891-897.doi: 10.12122/j.issn.1673-4254.2021.06.12

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联合检测粪便中ITGA4和SFRP2基因甲基化在大肠肿瘤诊断和预后中的价值

金 红，庞丽莹，李华洋，徐明鑫，闫海润，李荣辉   

  • 出版日期:2021-06-20 发布日期:2021-07-05

Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors

  • Online:2021-06-20 Published:2021-07-05

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摘要： 目的 探讨大肠肿瘤患者粪便中ITGA4和SFRP2基因甲基化水平在其疾病诊断和预后中的价值。方法 实时荧光定量PCR法检测结直肠癌（n=85）、结直肠腺瘤（n=65）和健康人（n=40）粪便中ITGA4和SFRP2基因甲基化水平。结果 3组年龄性别无明显差别,粪便ITGA4和SFRP2基因启动子甲基化在结直肠癌中的阳性检出率分别为48.2%和62.4%，联合检测的阳性检出率81.2%；在结直肠腺瘤中的阳性检出率分别为23.1%和43.1%，联合检测的阳性检出率69.2%。结直肠癌组ITGA4和SFRP2基因启动子甲基化阳性检出率明显高于结直肠腺瘤组（P<0.001，P=0.001）和健康对照组（P均<0.001），差异有统计学意义。而结直肠癌组术前ITGA4和SFRP2基因启动子甲基化水平与术后是否出现肿瘤复发有关；采用Kaplan-Meier法绘制无复发生存曲线，结果显示ITGA4和SFRP2基因启动子甲基化阳性患者组无复发生存率均明显低于阴性患者组（P=0.0002，P= 0.007）。其他因素均校正的情况下，经COX比例风险回归模型多因素分析，结果显示，术前ITGA4和SFRP2基因启动子甲基化和肿瘤分化程度与结直肠癌的复发有关（P=0.01，P=0.03），可以作为结直肠癌复发的独立危险因素。结论 基于粪便ITGA4和SFRP2基因甲基化单独检测的阳性检出率较低，而联合检测可以提高结直肠癌的阳性检出率，弥补了单独检测的不足。ITGA4 和SFRP2基因启动子甲基化和肿瘤分化程度可以作为结直肠癌复发的独立危险因素。

关键词: 大肠肿瘤；甲基化；粪便DNA

Abstract: Objective To investigate the value of quantitative detection of ITGA4 and SFRP2 gene methylation in stool DNA for the early diagnosis and prognostic evaluation of colorectal tumors. Methods Real-time PCR was used for quantitative assessment of ITGA4 and SFRP2 gene methylation levels in stool samples of 85 patients with colorectal cancer, 65 patients with colorectal adenoma and 40 healthy subjects. Results The 3 groups were comparable for age and gender composition. Methylated ITGA4 and SFRP2 promoters were detected in 48.2% and 62.4% of patients with colorectal cancer, respectively, with a combined positivity of 81.2%. ITGA4 and SFRP2 promoter methylation was detected in 23.1% and 43.1% of patients with colorectal adenoma, respectively, with a combined positivity of 69.2% . The positivity rates of ITGA4 and SFRP2 methylation were significantly higher in patients with colorectal cancer than in those with colorectal adenoma (P<0.001; P= 0.001) and healthy subjects (P<0.001; P<0.001). In colorectal cancer group, ITGA4 and SFRP2 promoter methylation levels were correlated with postoperative tumor recurrence in colorectal cancer group, and the relapse-free survival rate was significantly lower in positive patients for ITGA4 and SFRP2 promoter methylation than in the negative patients (P=0.0002; P=0.007). Multivariate analysis with the COX proportional hazard regression model showed that methylation of ITGA4 and SFRP2 gene promoters (P=0.01) and the degree of tumor differentiation (P=0.03) were associated with the recurrence of colorectal cancer, and were independent risk factors for the recurrence of colorectal cancer. Conclusions Combined detection of ITGA4 and SFRP2 gene methylation levels in stool DNA can improve the early diagnosis rate of colorectal tumor. ITGA4 and SFRP2 promoter methylation and the degree of tumor differentiation are independent risk factors for colorectal cancer recurrence.

Key words: colorectal tumor; methylation; stool DNA