骨肉瘤中RASSF1A基因的甲基化状态研究

目的：分析骨肉瘤组织中RASSF1A基因甲基化状况。方法：运用甲基化特异性PCR（MSP）分别检测44例骨肉瘤组织及相应的癌旁组织中RASSF1A基因启动子甲基化状态并分析其临床病理意义。结果：骨肉瘤组织中RASSF1A基因异常甲基化率（61.4%）显著高于癌旁正常骨组织中RASSF1A基因的异常甲基化率（20.5%）,二者之间差异具有统计学意义（P〈0.05）。RASSF1A基因异常甲基化导致组织中RASSF1A基因mRNA和蛋白表达水平均显著降低。另外,RASSF1A基因异常甲基化和肿瘤组织分化程度及全身有无转移情况有相关性（P值分别为0.022和0.016）,而与患者年龄、性别、肿瘤位置及大小等临床特征无关（P值分别为0.6944,0.977,0.786和0.831）。结论：RASSF1A基因启动子高甲基化可能是导致其在骨肉瘤中表达水平降低的分子机制之一,有望成为骨肉瘤早期辅助诊断的一个重要分子标志物。

Analysis of Methylation Status of RASSF1A Gene in Human Osteosarcoma

Objective：To investigate the methylation status of RASSF1A gene in human osteosarcomas.Methods：Methyla-tion-specific PCR（MSP） was used to detect the status of promoter hypermethylation of RASSF1A gene in 44 osteosarcoma and corre-sponding non-tumor bone tissues and the clinicopathological significance in human osteosarcoma was analyzed.Results：The methylation ratio of RASSF1A gene in osteosarcoma tissues（61.4%） was obviously higher than that in non-tumor bone tissues（20.5%,P0.05）.The abberant methylation of RASSF1A gene induced the decreased expression of RASSF1A mRNA and protein in osteosarcoma or non-tu-mor bone tissues.Additionally,the methylation of RASSF1A gene was significantly associated with tumor differentiation and metastasis（P=0.022 and 0.016,respectively）,but it had not associated with age,sex,tumor location and size of osteosarcoma patients（P=0.6944,0.977,0.786 and 0.831,respectively）.Conclusion：The methylation of RASSF1A gene may contribute to the decreased RASSF1A gene expression,and detection of RASSF1A promoter methylation might be an important molecular marker for the earlier auxiliary diagnosis of osteosarcoma.