RASSF2A基因的甲基化及表达在肾细胞癌中的作用

Research of renal cell carcinoma RASSF2A gene methylation and expression status

目的:探讨RASSF2A基因甲基化及mRNA的表达情况,并分析其与肾细胞癌的关系。方法:采用甲基化特异性聚合酶链反应(Methylation-Specific PCR,MSP)和逆转录-聚合酶链反应(Reverse Transcriptase-PCR,RT-PCR)来检测60例肾细胞癌患者癌组织及相应癌旁与正常组织中RASSF2A基因启动子甲基化状态及mRNA的相对表达量。结果:60例癌组织标本中的甲基化率较高,mRNA的相对表达量较低,其差异有统计学意义(P <0.05),在癌旁及正常组织中差异无统计学意义(P>0.05);在癌组织中,甲基化阳性患者mRNA的相对表达量低于甲基化阴性患者,有统计学差异(P <0.05)。肾细胞癌组织中β-catenin蛋白在细胞质中的表达率较高,具有统计学差异(P <0. 05),且RASSF2A基因甲基化与其表达呈正相关(相关系数为0.269,P <0.05)。结论:通过试验研究,我们发现在RCC中RASSF2A启动子区高甲基化的频发,其失活可能引起了基因的转录沉默,可能导致了β-catenin的表达较高,从而与RCC的发生、发展相关。

Objective: To investigate the renal cell carcinoma RASSF2A gene methylation and expression status of research,and to analyze the occurrence of renal cell carcinoma development in rats. Methods:Methylation specific polymerase chain reaction (Methylation-Specific PCR,MSP) and reverse transcription-polymerase chain reaction (Reverse Transcriptase-PCR,RT-PCR) to detect 60 cases of renal cell carcinoma patients,paraneoplastic RASSF2A normal tissue gene expression relative situation promoter methylation status and mRNA. Results: In the 60 cases,The methylation rate of cancer tissue was significantly higher than that of cancer paraneoplastic and normal tissues. The relative expression of RASSF2A gene mRNA was significantly lower than that of cancerous bypass and normal tissue. The difference was statistically significant (P <0.05).There was no significant difference between the methylation rate and the relative expression of mRNA (P >0.05);In the cancer tissue,the relative expression of mRNA in the methylation positive patients was lower than that of the mRNA in the negative methylation patients,and the difference was statistically significant (P < 0.05). There was positive correlation between RASSF2A gene methylation and protein expression of β-catenin in renal cell carcinoma tissues (r = 0.269,P <0.05). Conclusion: RASSF2A promoter hypermethylation is RCC frequent events,tumor suppressor gene RASSF2A inactivation may be one of the important reasons leading to transcriptional silencing,RASSF2A promoter hypermethylation and mRNA expression decrease may be involved in the RCC the occurrence and development. RASSF2A gene methylation might be related to the high expression of β-catenin gene. It had effect on the invasion and metastasis of renal cell carcinoma through changing the intracellular distribution of β-catenin. It indicated that this signaling pathway was involved in tumorigenesis.