RASSF10基因在贲门腺癌组织中的甲基化状态及表达

Methylation status and expression of RASSF10 gene in gastric cardia adenocarcinoma

背景与目的:Ras相关域家族10基因(Ras-association domain family 10,RASSF10)在多种肿瘤组织中具有肿瘤抑制功能,然而在贲门腺癌组织中的研究尚未见报道。检测贲门腺癌(gastric cardia adenocarcinoma,GCA)组织中RASSF10基因的甲基化状态及表达情况,进一步探讨RASSF10基因在GCA发生、发展中的作用。方法:分别应用甲基化特异性聚合酶链式反应(methylation specific polymerase chain reaction,MSP)、逆转录-聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)及免疫组织化学方法检测81例GCA患者癌组织及癌旁正常组织中RASSF10基因的甲基化状态及mRNA和蛋白表达情况。结果:RASSF10基因在GCA组织中的启动子区甲基化率(64.2%,52/81)显著高于癌旁正常组织(21.0%,17/81,P<0.05),并与肿瘤组织的TNM分期、分化程度及淋巴结转移相关(P均<0.05)。RASSF10基因在GCA组织中的mRNA表达量(0.57±0.05)显著低于癌旁正常组织(0.78±0.02,P<0.05),并与肿瘤组织的TNM分期及淋巴结转移相关(P均<0.05)。RASSF10蛋白在GCA组织中的阳性表达率(31.1%,26/81)明显低于癌旁正常组织(71.6%,58/81,P<0.05),并与肿瘤组织的TNM分期、分化程度及淋巴结转移相关(P均<0.05)。RASSF10基因在GCA组织中的甲基化率与其蛋白表达呈明显的负相关。结论:RASSF10基因启动子区的异常高甲基化导致的基因沉默可能是GCA发生的机制之一。

Background and purpose：RASSF10 acts as a kind of tumor suppressor in various tumor tissues, but researches in cardiac adenocarcinoma has not been reported. This study aimed to detect the methylation status and expression ofRas-association domain family 10 （RASSF10） in gastric cardia adenocarcinoma （GCA）, and explore its role in occurrence and development of GCA.Methods：Methylation speciifc polymerase chain reaction （MSP）, reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry method were respectively used to detect methylation status, mRNA expression and protein expression ofRASSF10 in 81 GCA tissues and corresponding normal tissues.Results：The promoter methylation frequency ofRASSF10 in GCA tissues （64.20%, 52/81） was signiifcantly higher than that in corresponding normal tissues （20.99%, 17/81,P〈0.05）, and was closely correlated with TNM stages, differential degree and lymph node metastasis （P〈0.05）. RASSF10 mRNA expression in GCA tissues （0.57±0.05） was significantly lower than that in corresponding normal tissues （0.78±0.02,P〈0.05）, and was closely correlated with TNM stages and lymph node metastasis （P〈0.05）. Protein expression of RASSF10 in GCA tissues （31.10%, 26/81） was signiifcantly lower than that in corresponding normal tissues （71.60%, 58/81,P〈0.05）, and was closely correlated with TNM stages, differential degree and lymph node metastasis （P〈0.05）. The promoter methylation frequency ofRASSF10 in GCA tissues was inversely related to its protein expression.Conclusion：Inactivation of RASSF10 caused by aberrantmethylation in the promoter region may be closely correlated with the GCA tumorgenesis.