喉鳞癌中凝血酶敏感蛋白1的表达及其基因启动子甲基化分析  

The expression of thrombospondin 1 and its gene hypermethylation in laryngeal squamous cell cancer

作　　者：黄闯[1] 何云[1] 葛家华[1] 陈鸿雁[2] 周晓红[1] 

机构地区：[1]重庆市肿瘤研究所头颈外科,重庆400030 [2]重庆医科大学附属第一医院耳鼻咽喉科,重庆400016

出　　处：《肿瘤》2014年第3期264-270,共7页Tumor

基　　金：重庆市医学科研计划项目(编号:2012-2-494)

摘　　要：目的 :检测喉鳞癌组织中凝血酶敏感蛋白1(thrombospondin 1,THBS1)基因的mRNA、蛋白表达水平和启动子甲基化状态,并分析它们与临床病理特征的相关性。方法 :取66例喉鳞癌及其癌旁组织,应用反转录PCR及蛋白质印迹法分别检测THBS1 mRNA及蛋白的表达水平,并用单因素方差分析和t检验分析其与临床病理特征的相关性;应用甲基化特异性PCR检测THBS1基因启动子区甲基化水平,并用χ2检验分析其与临床病理特征的相关性。结果 :喉鳞癌组织中THBS1 mRNA及蛋白表达水平均显著低于其在癌旁组织中的表达水平(P<0.05),且均与喉鳞癌患者淋巴结转移及TNM分期有关(P<0.05);喉鳞癌组织中THBS1基因甲基化率(48.50%±6.15%)显著高于癌旁组织中的甲基化率(6.06%±2.92%)(P<0.05)。癌组织中THBS1基因高甲基化率与THBS1 mRNA及蛋白水平的表达降低、淋巴结转移及TNM分期有关(P<0.05)。结论 :喉鳞癌中存在THBS1 mRNA及蛋白异常低表达和基因启动子区高甲基化,而且它们与喉鳞癌的临床进展有关。Objective： To explore the mRNA and protein expressions of thrombospondin 1 （THBS1） gene and the DNA methylation of its promoter in laryngeal squamous cell cancer （LSCC）, and to analyze their relationship to clinicopathological features of LSCC. Methods： Sixty-six pairs of fresh LSCC tissues and the matching adjacent normal tissues were taken from 66 cases of LSCC. The mRNA and protein expressions of THBS1 gene were detected by revere transcription PCR and Western blotting assay, respectively. Then their relationship to clinicopathological features of LSCC was analyzed by one-way ANOVA and t test. The methylation of THBSl gene promoter was detected by the DNA methylation specific PCR, and its relationship to clinicopathological features of LSCC was analyzed by Zz test. Results： The mRNA and protein expressions of THBS1 gene in LSCC tissues were significantly decreased as compared with those in the adjacent normal tissues （P 〈 0.05）, and these expressions were also associated with lymph node involvement and TNM staging （P 〈 0.05）. The positive rate of the hypermethylation of THBS1 gene in the LSCC tissues （48.50%_＋6.15%） was significantly higher than that in the matching adjacent normal tissues （6.06%_＋2.92%） （P 〈 0.05）. The mRNA and protein expressions of THBS1 gene were associated with the hypermethylation of its gene promoter （P 〈 0.05）. THBS1 gene hypermethylation status in LSCC tissues was associated with lymph node involvement and TNM staging （P 〈 0.05）. Conclusion： The decreased expressions of THBS1 mRNA and protein and the high methylation of its gene promoter may play crucial roles in carcinogenesis and development of LSCC.

关 键 词：喉肿瘤 凝血酶敏感蛋白1 DNA甲基化 基因表达 肿瘤分期 淋巴结转移 

分 类 号：R739.65[医药卫生—肿瘤]