崔建利, 郭炜, 郭艳丽, et al. Methylation status and expression of RASSF10 gene in gastric cardia adenocarcinoma[J]. China Oncology, 2014, 24(8): 568-574. DOI: 10.3969/j.issn.1007-3969.2014.08.002.
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,P0.05),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,P0.05),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,P0.05),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。
Abstract
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 of Ras-association domain family 10 (RASSF10) in gastric cardia adenocarcinoma (GCA)
and explore its role in occurrence and development of GCA. Methods: Methylation specific 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 of RASSF10 in 81 GCA tissues and corresponding normal tissues.Results: The promoter methylation frequency of RASSF10 in GCA tissues (64.20%
52/81) was significantly higher than that in corresponding normal tissues (20.99%
17/81
P0.05)
and was closely correlated with TNM stages
differential degree and lymph node metastasis (P0.05). RASSF10 mRNA expression in GCA tissues (0.57±0.05) was significantly lower than that in corresponding normal tissues (0.78±0.02
P0.05)
and was closely correlated with TNM stages and lymph node metastasis (P0.05). Protein expression of RASSF10 in GCA tissues (31.10%
26/81) was significantly lower than that in corresponding normal tissues (71.60%
58/81
P0.05)
and was closely correlated with TNM stages
differential degree and lymph node metastasis (P0.05). The promoter methylation frequency of RASSF10 in GCA tissues was inversely related to its protein expression.Conclusion: Inactivation of RASSF10 caused by aberrant methylation in the promoter region may be closely correlated with the GCA tumorgenesis.