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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。
Objective: To analyze the methylation status of RASSF1A gene in osteosarcoma. Methods: Methylation-specific PCR (MSP) was used to detect the methylation status of RASSF1A promoter in 44 osteosarcoma tissues and corresponding paracancerous tissues, respectively, and to analyze the clinicopathological significance. Results: The abnormal methylation rate of RASSF1A gene in osteosarcoma (61.4%) was significantly higher than that in normal paracancerous tissues (20.5%), the difference was statistically significant (P <0.05). Aberrant methylation of RASSF1A resulted in a significant reduction of RASSF1A mRNA and protein expression in the tissues. In addition, the abnormal methylation of RASSF1A gene correlated with the degree of tumor differentiation and systemic metastasis (P = 0.022 and 0.016, respectively), but not with clinical features such as age, sex, tumor location and size 0.6944, 0.977, 0.786 and 0.831 respectively). CONCLUSION: Hypermethylation of RASSF1A gene promoter may be one of the molecular mechanisms leading to its decreased expression in osteosarcoma, which may be an important molecular marker for early diagnosis of osteosarcoma.