脆性位点基因WWOX mRNA在肝细胞癌中的表达及临床病理意义  

Expression of Fragile Gene WWOX mRNA and its Clinicopathological Significance in Heptocellular Carcinoma

作　　者：王斌[1] 林洁[2] 罗顺锋[3] 汪晓军[1] 黄爱民[1] 

机构地区：[1]福建医科大学基础医学院病理学系肿瘤研究室,福州350004 [2]福建医科大学省立临床医学院福建省立医院病理科,福州350001 [3]福建医科大学附属第一医院肝病中心肝外科,福州350005

出　　处：《福建医科大学学报》2011年第6期393-397,共5页Journal of Fujian Medical University

基　　金：卫生部科学研究基金-福建省卫生教育联合攻关计划项目(WKJ2008-2-63);福建省自然科学基金(2008J0286)

摘　　要：目的检测WWOX野生型mRNA及其异常转录剪接体在肝细胞癌中的表达情况,并分析其临床病理意义。方法采用Rea-ltime RT-PCR和RT-PCR方法检测44例肝细胞癌(HCC)、相应癌旁肝组织和5例正常肝组织中WWOX野生型mRNA及转录剪接体Variant1、Variant4及Variant6的表达,同时分析WWOX mRNA的表达与临床病理参数的关系。结果 (1)在HCC中,WWOX野生型mRNA的表达较癌旁肝组织明显降低(P<0.01);随着HCC组织学分级的升高和分化程度的降低,WWOX野生型mRNA的表达量逐步减少(P<0.05);术后复发组WWOX野生型mRNA的表达低于非复发组(P<0.05)。(2)通过RT-PCR方法检测到了WWOX异常转录剪接体Variant4和Variant6,并经过测序证实;Variant4在HCC中的出现率为70.5%,明显高于癌旁肝组织的38.6%和正常肝组织的40%(P<0.01),其表达在肝硬化和无肝硬化组中有差别(P<0.05);Vari-ant6在HCC、癌旁肝组织、正常肝组织中的检出率分别为72.7%,81.8%和80.0%(P<0.05);这两型异常转录剪接体的出现与HCC的大小、组织学类型、组织学分级、分化、血管侵犯、包膜破坏、卫星病灶等病理特征及患者的性别、甲胎蛋白水平、复发情况均无关。结论 WWOX野生型mRNA表达的下调可能在HCC的发生发展中起重要作用;WWOX异常转录剪接体Variant4可能为致癌因素致癌作用的一个分子靶点。Objective To investigate the expression of WWOX wild-type mRNA and aberrant transcripts and the clinicopathological features in hepatocellular carcinoma（HCC）.Methods The expression of WWOX wild-type mRNA and transcript Variant1,Variant4 and Variant6 were detected by Real-time RT-PCR and RT-PCR in 44 HCC samples,adjacent liver tissue samples and 5 normal liver tissue samples.Results（1） The expression of the wild-type WWOX gene was significantly lower（P〈0.01） than the adjacent liver tissues,which decreased with the tumor grade increased and differentiation decreased in HCC（P〈0.05）.The expression of the wild-type WWOX mRNA in HCC with recrudesce was lower than that in those without recrudesce（P〈0.05）.（2）The aberrant transcripts Variant4 and Variant6 were detected by RT-PCR and were confirmed by gene sequencing.Variant4 was detected in 70.5% HCCs,38.6% adjacent liver tissues and 40% normal liver tissues（P〈0.01）.The occurrence of variant4 had a significant association with cirrhosis（P〈0.05）.Variant6 was detected in 72.7% HCCs,81.8% adjacent liver tissues and 80% normal liver tissues（P〈0.05）.The expression of Variant4 and Variant6 were not associated with gender,AFP level,tumor size,histological type,grade,vascular invasion,capsular invasion,satellites formation and recrudesce（P〉0.05）.Conclusion The decreased expression of WWOX gene may be important during tumorigenesis in HCC.The aberrant transcript variant4 of WWOX gene might be a molecular target of carcinogens.

关 键 词：癌 肝细胞癌 RNA 信使 基因 肿瘤抑制 染色体脆性位点 逆转录聚合酶链反应 聚合酶链反应 

分 类 号：R735.7[医药卫生—肿瘤]