鼻咽癌组织FHIT、WWOX基因表达变化及其原因探讨  

Expression changes of FHIT and WWOX gene in nasopharyngeal carcinoma and the mechanism

作　　者：黄春妮[1] 莫武宁[1] 黄健[1] 李屏[2] 刘磊[1] 杨峥[1] 

机构地区：[1]广西医科大学第一附属医院,南宁530021 [2]广西中医药大学第一附属医院

出　　处：《山东医药》2016年第26期20-23,共4页Shandong Medical Journal

基　　金：广西壮族自治区卫生厅科研基金资助项目(Z2013024)

摘　　要：目的 观察鼻咽癌组织中脆性组氨酸三联体（FHIT）基因和WW结构域氧化还原酶（WWOX）基因表达变化,并探讨其原因。方法 选择89例鼻咽癌患者为观察组,取其手术切除的鼻咽癌组织标本和血液标本;61例慢性鼻黏膜炎患者为对照组,留取其鼻咽部黏膜组织标本以及血液标本。采用RT-PCR法检测观察组鼻咽癌组织和对照组鼻咽部黏膜组织FHIT mRNA、WWOX mRNA及启动子甲基化情况。用MSP法检测两组患者血液中FHIT、WWOX基因杂合性缺失情况。结果 观察组FHIT、WWOX mRNA相对表达量低于对照组（P均〈0.05）。观察组临床分期Ⅲ~Ⅳ期者FHIT、WWOX mRNA相对表达量低于Ⅰ~Ⅱ期者（P均〈0.05）。观察组鼻咽癌患者临床分期与FHIT、WWOX mRNA相对表达量呈负相关（r分别为-0.731、-0.816,P均〈0.05）。观察组FHIT、WWOX基因启动子甲基化程度分别为0.46±0.34、0.37±0.28,高于对照组的0.15±0.17、0.11±0.09,P均〈0.05。Spearman相关分析显示观察组FHIT、WWOX mRNA与该基因启动子甲基化程度呈负相关（r分别为-0.689、-0.594,P均〈0.05）。观察组39例（43.8%）存在至少1个FHIT基因位点杂合性缺失,42例（47.2%）存在至少1个WWOX基因位点杂合性缺失,明显高于对照组的3例（4.9%）和2例（3.3%）,P均〈0.05。观察组FHIT、WWOX mRNA与该基因基因杂合性缺失存在负相关（r分别为-0.239、-0.364,P均〈0.05）。结论 鼻咽癌的发生、发展与FHIT、WWOX基因的表达下调有关,而引起鼻咽癌组织FHIT、WWOX表达下调的原因可能是该基因启动子甲基化和杂合性缺失,其中基因启动子甲基化可能是导致其表达下调的主要原因。Objective To observe the expression changes of FHIT gene and WWOX gene in nasopharyngeal carcino-ma and to explore the mechanism.Methods We chose 89 patients with nasopharyngeal carcinoma as the experimental group,and took their surgical removal of the nasopharyngeal carcinoma tissue specimens and blood specimens;and 61 pa-tients with chronic nasal mucosal inflammation as the control group,and took their nasopharyngeal mucosa tissue specimens and blood specimens.RT-PCR was used to detect the expression of FHIT mRNA,WWOX mRNA and promoter methylation in nasopharyngeal carcinoma tissue specimens of the experimental group and nasopharyngeal mucosa tissue specimens of the control group.MSP was used to detect loss of heterozygosity （LOH）of FHIT and WWOX genes from blood specimens in the two groups.Results The relative expression of FHIT mRNA and WWOX mRNA in the experimental group was signifi-cantly lower than that in the control group （all P 〈0.05）.The relative expression of FHIT mRNA and WWOX mRNA in clinical stage Ⅲ ～Ⅳ was significantly lower than that in clinical stage Ⅰ-Ⅱ of the experimental group （all P 〈0.05）.In the experimental group,clinical stage was negatively correlated with the relative expression of FHIT and WWOX mRNA （r=-0.731,-0.816,all P 〈0.05）.FHIT and WWOX gene promoter methylation degree in the experimental group were 0.46 ±0.34 and 0.37 ±0.28,higher than 0.15 ±0.17 and 0.11 ±0.09 in the control group （all P 〈0.05）.Spearman correlation analysis showed that the FHIT and WWOX mRNA was negatively correlated with the degree of the gene promoter methylation in the experimental group （r =-0.689, -0.594,all P 〈0.05 ）.In the experimental group,39 cases （43.8%）had at least 1 LOH in the FHIT gene and 42 cases （47.2%）had at least 1 LOH in the WWOX gene,which significantly higher than 3 cases （4.9%）and 2 cases （3.3%）of the control group （all P 〈0.05 ）.The FHIT and WWOX mRNA was negatively correlated with gene LOH in the experimental group �

关 键 词：鼻咽癌 脆性组氨酸三联体基因 WW结构域氧化还原酶基因 启动子甲基化 

分 类 号：R739.63[医药卫生—肿瘤]