外周血USP1基因甲基化与大肠癌预后风险的关系

Relationship between methylation of USP1 gene in peripheral blood and prognosis risk of colorectal cancer

目的探讨外周血中去泛素化酶USP1甲基化及临床特征与大肠癌预后风险的关系。方法采用队列研究,共纳入286例大肠癌患者。使用高分辨率熔解曲线分析法(HRM)检测基因甲基化水平。应用Cox回归模型评估基因甲基化及临床特征与大肠癌预后风险之间的关联。结果在男性大肠癌病例中,USP1甲基化增加预后不良风险(HR=2.091,95%CI:1.195~3.661,P=0.010)。临床病理特征中,UICC肿瘤分期4期(HR=2.464,95%CI:1.205~5.039,P=0.014)、肿瘤大小超过50mm(HR=1.610,95%CI:1.016~2.550,P=0.043)和组织学非腺型(HR=5.117,95%CI:1.142~22.930,P=0.033)是大肠癌不良预后风险增加的影响因素。结论UICC肿瘤分期4期、肿瘤大小超过50mm和组织学分型为非腺型会增加大肠癌不良预后风险。外周血USP1基因启动子区甲基化与男性大肠癌预后不良风险增加有关。

Objective The objective of this study was to investigate the relationship between the methylation and clinical features of deubiquitinating enzyme USP1 in peripheral blood and the prognosis risk of colorectal cancer.Methods A total of 286 patients with colorectal cancer were enrolled in the cohort study.The level of DNA methylation status of USP1 was detected using high resolution melting curve analysis(HRM).The Cox regression model was used to assess the association between USP1 methylation and clinical features and prognosis risk of colorectal cancer.Results In male colorectal cancer cases,USP1 methylation could incerease the risk of colorectal cancer with poor pregnosis( HR =2.091,95% CI :1.195~3.661, P =0.010).Among the clinicopathological features,UICC tumor stage 4( HR =2.464,95% CI :1.205~5.039, P =0.014),tumor size over 50 mm( HR =1.610,95% CI :1.016 ~2.550, P =0.043)and histological non-adenotype( HR =5.117,95% CI :1.142~22.930, P =0.033)were contributing factors to the increased risk of colorectal cancer with poor pregnosis.Conclusion UICC tumor stage 4,tumor size over 50 mm and histological non-adenotype will increase the risk of colorectal cancer with poor pregnosis.The methylation of promoter region of USP1 gene in peripheral blood is associated with an increased risk of poor pregnosis in male colorectal cancer.