摘要目的 探讨结肠癌中抑癌基因Rap1GTP酶激活蛋白(Rap1GAP)启动子甲基化情况,为结肠癌的早期诊断、早期治疗、靶向治疗及改善预后等提供理论依据及研究方向.方法 回顾性分析山西省忻州市人民医院病理科2010年1月至2014年9月病理诊断为结肠腺癌的患者33例,其中男性19例,女性14例,年龄41~72岁,取手术切除石蜡包埋标本.选取同期16例结肠腺瘤患者的石蜡包埋标本,包括男性9例,女性7例,年龄34~58岁.选取肿瘤远端(距肿瘤>15 cm)切缘正常组织13例.使用定量甲基化特异性聚合酶链反应(q-MSP)技术检测Rap1GAP基因启动子区甲基化水平.比较3种组织间及临床病理因素亚组间Rap1GAP基因启动子区甲基化水平的差异.结果 Rap1GAP启动子甲基化率[中位数(四分位数间距)]在结肠癌、结肠腺瘤和癌旁正常组织中分别为65.43%(50.35%)、21.37%(8.39%)、17.43%(15.71%),结肠癌组高于结肠腺瘤组及癌旁正常组织组,差异有统计学意义(P<0.05).结肠癌组男性、女性Rap1GAP启动子甲基化率分别为42.74%(70.44%)、21.98%(80.00%);≤60岁与>60岁分别为36.26%(62.62%)、26.23%(76.42%);高分化癌、中低分化癌分别为21.98%(40.32%)、42.74%(74.20%);TNMⅠ~Ⅱ期、Ⅲ~Ⅳ期分别为25.31%(48.27%)、36.26%(75.55%).结肠癌中Rap1GAP甲基化率与患者年龄、性别、肿瘤分化程度、TNM分期均无关(均P>0.05).结论 Rap1GAP启动子甲基化可能与结肠癌的发生、发展有关,可能作为结肠癌早期诊断的靶标.

abstractsObjective To explore the methylation status of Rap1 GTPase activating protein (Rap1GAP) promoter in colon cancer, and to provide the oretical basis and research direction for the early diagnosis, targeted therapy, anti-multidrug resistance of colon cancer and so on. Methods The paraffin embedded specimens of 33 patients with colonic adenocarcinoma diagnosed by pathology were analyzed from Department of Pathology of Xinzhou City People′s Hospital from January 2010 to September 2014, including 19 males and 14 females, and aged 41-72 years old. The paraffin embedded specimens of 16 patients with colonic adenoma were enrolled, including 9 males and 7 females, and aged 34-58 years old. 13 normal tissues from the tumor distal margin (from the tumor > 15 cm) were selected. Quantitative methylation specific PCR (q-MSP) was applied to detect methylation level of Rap1GAP gene promoter. The methylation level differences of Rap1GAP gene promoter region among 3 groups or between different clinicopathologic factor subgroups were compared. Results The methylation rates [median (interquartile range)] of Rap1GAP promoter were 65.43 % (50.35 %), 21.37 % (8.39 %) and 17.43 % (15.71 %) in colonic adenocarcinoma group, colonic adenoma group and adjacent normal tissue group, respectively. The methylation rate of colonic adenocarcinoma group was significantly higher than that of colon adenoma group or that of adjacent normal tissue group (P< 0.05). The methylation rates of Rap1GAP promoter in colonic adenocarcinoma were not correlation with age, sex, differentiation and the stage of TNM [ male vs. female: 42.74 % (70.44 %) vs. 21.98%(80.00%);≤60yearsoldvs.>60yearsold:36.26%(62.62%)and26.23%(76.42 %);well-differentiated vs. moderately/poorly-differentiated: 21.98 % (40.32 %) vs. 42.74 % (74.20 %); TNM Ⅰ-Ⅱ vsⅢ-Ⅳ: 25.31 % (48.27 %) vs. 36.26 % (75.55 %); all P> 0.05]. Conclusion The methylation status of RAP1GAP promoter maybe associate with genesis and development of colon cancer, which might be used as a target for early diagnose of colon cancer.