肺癌中FHIT基因异常甲基化及其蛋白表达的意义  

The aberrant methylation of fragile histidine triad(FHIT) gene and its significance of the expression of FHIT protein in lung cancer

作　　者：杨志慧[1] 刘惠敏[1] 何金[1] 王良哲[1] 孙静[1] 陈兵[1] 

机构地区：[1]第二军医大学附属长征医院病理科,上海200003

出　　处：《肿瘤》2007年第11期902-906,共5页Tumor

摘　　要：目的:检测肺癌组织FHIT蛋白表达及基因异常甲基化,探讨其在肺癌发生发展中的作用。方法:应用免疫组化SP法和甲基化特异性PCR(MSP)检测肺癌组织与癌旁组织(n=60)中FHIT蛋白表达和基因异常甲基化情况,并对基因甲基化扩增产物进行测序,对60例患者随访调查。结果:FHIT蛋白在癌旁组织的阳性表达明显高于癌组织,二者差异存在统计学意义(76.7%vs50.0%,P<0.05);FHIT基因异常甲基化在癌组织中的发生率明显高于癌旁组织,二者差异存在统计学意义(68.3%vs35.0%,P<0.001);FHIT基因甲基化的发生率在FHIT蛋白阴性患者中高于阳性表达者(83.3%vs53.5%,P<0.05);FHIT蛋白表达及基因甲基化发生率均与性别、年龄、吸烟状况、组织学类型、大体分型、TNM分期及淋巴结转移无关(P>0.05);FHIT蛋白阳性表达患者生存率高于阴性表达者(P<0.05),FHIT蛋白是影响无瘤生存时间的危险因素(P<0.001)。结论:肺癌中FHIT基因异常甲基化频繁发生,FHIT蛋白表达明显下调,FHIT在肺癌的发生发展中可能具有重要的作用,FHIT蛋白可以作为判断患者预后的重要指标。Objective： To detect the expression of fragile histidine triad （FHIT）protein and aberrant methylation of its gene in lung carcinoma tissue and discuss their significance in tumorigenesis of lung cancer. Methods： The expression of FHIT protein was determined by immunohistochemical SP staining and its aberrant methylation was detected by methylation-specific PCR （MSP） in lung cancer and adjacent lung tissues （ n = 60）. The sequencing of the amplified products of MSP was performed. The 60 patients were followed up. Results： The expression of FHIT protein in adjacent lung tissues was obviously higher than that in lung cancer tissues. There was significant difference between them （76.7% vs 50%, P 〈0.05 ）. The aberrant methylation of FHIT gene was significantly higher in lung cancer tissues than that in adjacent lung tissues （68.3% vs 35.0%, P 〈0. 001 ）. And the aberrant methylation of FHIT gene occurred frequently in FHIT-negative patients compared with FHIT-positive patients （83.3% vs 53.5%, P 〈0.05 ）. The expression of FHIT protein and the aberrant methylation of FHIT gene had no correlation with clinicopathological parameters （ age, sex, smoking status, histological type, general classification, TNM staging, and lymph node metastasis） in the patients with lung cancer （ P 〉 0. 05 ）. The survival time was longer in FHIT-positive patients than FHIT-negative patients （ P 〈 0. 05 ）. The FHIT protein was the risk factor associated with the disease-free survival time of patients （ P 〈 0. 01 ）. Conclusion： The aberrant methylation of FHIT gene occurrs frequently and the expression of FHIT protein is significantly down-regulated in lung cancer. FHIT may play an important role in the tumorigenesis and development of lung cancer. FHIT protein could be used as an important factor for predicting the prognosis of patients.

关 键 词：肺肿瘤 脆性组氨酸三联体 DNA甲基化 基因表达 

分 类 号：R734.2[医药卫生—肿瘤]