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目的:研究鼻咽鳞癌组织中的抑癌基因RASSF1A的表达及其基因启动子区异常甲基化的情况。并分析DNA异常甲基化与鼻咽鳞癌临床病理因素之间的关系。方法:利用RT-PCR和MS-PCR的方法,分析38例鼻咽鳞癌组织标本、10例鼻咽炎性组织标本、4例正常鼻咽黏膜组织标本、两种鼻咽癌细胞株中RASSF1A基因的表达和其基因启动子区异常甲基化的情况。采用甲基化抑制剂5-Aza-CdR处理鼻咽癌细胞株,观察RASSF1A重新表达的情况。结果:38例鼻咽癌组织标本和两种细胞株的RASSF1A基因表达显著低于对照组(P<0.05);71.05%的鼻咽癌标本及两种鼻咽癌细胞株发生异常甲基化;甲基化与年龄、性别、临床分期和颈部淋巴结转移无相关性(P>0.05),与RASSF1A基因表达和肿瘤分化程度有关(P<0.05);用5-Aza-CdR处理的低表达RASSF1A基因的鼻咽癌细胞株,RASSF1A基因表达上调。结论:鼻咽癌患者肿瘤组织中存在RASSFIA基因的表达下调现象,基因转录启动区的异常甲基化是导致鼻咽癌组织中RASSF1A基因表达下调的主要原因。
OBJECTIVE: To study the expression of RASSF1A gene and the abnormal methylation of its promoter region in nasopharyngeal squamous cell carcinoma. And analyze the relationship between DNA abnormal methylation and clinicopathological factors of nasopharyngeal squamous cell carcinoma. Methods: Thirty-eight nasopharyngeal squamous cell carcinoma specimens, 10 nasopharyngeal inflammatory tissue specimens and 4 normal nasopharyngeal mucosa specimens were analyzed by RT-PCR and MS-PCR. RASSF1A gene The expression of its gene promoter region and abnormal methylation of the situation. Nasopharyngeal carcinoma cell lines were treated with methylation inhibitor 5-Aza-CdR to observe the re-expression of RASSF1A. Results: The expression of RASSF1A gene in 38 nasopharyngeal carcinoma tissues and two cell lines was significantly lower than that in the control group (P <0.05). Abnormal methylation was found in 71.05% of nasopharyngeal carcinoma specimens and two nasopharyngeal carcinoma cell lines. There was no correlation between methylation and age, sex, clinical stage and cervical lymph node metastasis (P> 0.05), and was correlated with the expression of RASSF1A gene and the degree of tumor differentiation (P <0.05). Low expression of RASSF1A Gene nasopharyngeal carcinoma cell line, RASSF1A gene expression upregulation. CONCLUSIONS: The down-regulation of RASSFIA gene expression exists in the tumor tissues of nasopharyngeal carcinoma patients. Aberrant methylation of the gene transcription initiation region is the main reason for the down-regulation of RASSF1A gene expression in NPC tissues.