RASSF10基因在贲门腺癌组织中的甲基化状态及表达

摘要

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.