摘要
背景与目的:目前认为CpG岛甲基化导致转录抑制是恶性肿瘤发生的重要机制之一。微管抑制剂诱发有丝分裂应激时,CHFR基因能够控制细胞分裂的进行。本研究检测胃癌中CHFR基因启动子区甲基化状态,探讨该基因甲基化状态与胃癌临床病理特征的关系;并比较甲基化特异性PCR方法(methylation-specific polymerase chain reaction,MSP)和结合重亚硫酸盐的限制性内切酶法(combined bisulfite restriction analysis,COBRA)在检测胃癌组织CHFR基因甲基化状态的差异性。方法:首先采用MSP方法检测64例胃癌患者胃癌组织和相对应的癌旁正常组织中CHFR基因启动子区的甲基化状态,然后采用COBRA方法检测64例胃癌患者胃癌组织中CHFR基因启动子区的甲基化状态,并将检测结果结合各病例的临床特征进行分析。结果:MSP方法检测结果显示,51.6%的胃癌组织和18.8%的癌旁正常组织中存在CHFR基因异常甲基化,两者之间的差异有统计学意义(P<0.001);CHFR基因启动子区异常甲基化状态在不同临床病理学特征(包括年龄、性别、肿瘤大小、病理分期、Borrman分型、肿瘤浸润深度、组织分化程度和淋巴转移程度)的胃癌组织和癌旁组织中的差异无统计学意义(P值均>0.05)。COBRA方法检测结果显示,肿瘤组织CHFR甲基化阳性率为42.2%(27/64),与MSP方法检测结果的差异无统计学意义(P>0.05)。结论:CHFR基因异常甲基化是胃癌发生过程中的频发事件,检测胃黏膜组织中CHFR基因异常甲基化状态可能有助于胃癌的诊断。对于胃癌组织CHFR基因启动子区甲基化的检测,MSP与COBRA两种方法没有明显差异。
Background and Objective: Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation-specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer. Methods. Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0. Results: The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P〈 0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age,gender, tumor size, clinical stage, Borrman type, tumor invasion depth, differentiation, and lymph node metastasis (P〉 0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P〉 0.05). Conclusions. Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene in gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2010年第2期171-175,共5页
Chinese Journal of Cancer
基金
国家自然科学基金项目(No.30672383)~~
关键词
CHFR基因
甲基化
胃肿瘤
甲基化特异性PCR
结合重亚硫酸盐的限制性内切酶法
CHFR gene, methylation, gastric neoplasm, methylation-speciticpolymerase chain reaction (MSP), combined bisulfite restriction analysis(COBRA)