声门上型喉癌组织中的BRMS1蛋白表达及甲基化的研究

目的:探讨声门上型喉鳞状细胞癌组织中乳腺癌转移抑制基因(BRMS1)的蛋白表达以及BRMS1基因启动子区域甲基化情况及其临床意义。方法:采用Western blotting法检测70例声门上型喉癌组织原发灶、60例癌旁正常喉黏膜组织和44例颈部淋巴结转移灶中BRMS1蛋白的表达情况;甲基化特异聚合酶链反应(MSP)法检测上述组织中的BRMS1基因启动子区域甲基化情况,探讨BRMS1基因启动子甲基化与其基因表达的相关性;分析BRMS1蛋白表达及BRMS1基因启动子甲基化情况与患者的临床分期、病理分级、颈部淋巴结转移等方面的相关分析。结果:Western blotting检测发现声门上型喉癌原发灶、癌旁正常喉黏膜组织和颈部淋巴结转移灶均有BRMS1蛋白表达,在癌组织及转移淋巴结中BRMS1蛋白表达下调(P<0.05)。MSP法检测发现BRMS1基因启动子区甲基化,在BRMS1蛋白低表达患者的原发灶中检测到34例BRMS1基因启动子区甲基化,44例BRMS1蛋白低表达的颈部淋巴结转移灶中检测到32例BRMS1基因启动子区甲基化,60例癌旁正常喉黏膜组织中均未检测到BRMS1基因启动子区甲基化,统计学分析结果表明在声门上型喉癌中BRMS1基因启动子甲基化与其基因表达下调密切相关(rs=0.66,P<0.05)。结论:声门上型喉癌组织中BRMS1蛋白表达下调。BRMS1蛋白表达下调与声门上型喉癌的P-TNM分期、病理分化程度和颈部淋巴结转移密切相关。BRMS1基因启动子甲基化与声门上型喉癌组织中BRMS1基因表达下调相关,也可能是声门上型喉癌组织中BRMS1基因表达下调的原因之一。

The study of expression of BRMS1 gene protein and the expression of BRMS1 gene promotor area methylation in supraglottic laryngeal carcinoma and its clinical significance

Objective:To investigate the expression of breast cancer metastasis suppressor 1(BRMS1)gene protein and the expression of BRMS1 gene promotor area methylation in supraglottic cancer and to evaluate its clinical significance.Method:The expression of BRMS1 protein and BRMS1 gene promotor area methylation were examined by using Western blotting method and methylation-specific polymerase chain reaction(MSP) method in 70 cases of supraglottic cancer tissues and 60 cases of their surrouding laryngeal normal mucosa tissues(LNT) and 44 cases of cervical lymph node metastasis of supraglottic cancer.Result:Western blot results indicate that BRMS1 protein expression is declined expression level in supraglottic cancer tissue than the expression of BRMS1 protein in LNT of supraglottic cancer.Compared with paracarcinoma normal laryngeal mucous tissue,BRMS1 gene protein in supraglottic cancer tissue primary lesion decreased obviously,and it is decreased more obviously in cervical lymph node metastasis lesion,the discrepancy is notable(P<0.05).MSP results indicate BRMS1 gene promotor methylation is coordinated with its down-expression in supraglottic cancer tissue.BRMS1 promotor area methylation analysis reveal that there were 34 patients with methylation in 70 patients′ supraglottic cancer tumor primary lesion,hold 48.6%(34/70);32 patients have methylation in 44 patients′ cervical metastasis lymph node tissue,hold 72.7%(32/44);however,there is no methylation in 60 paracarcinoma tissue(rs=0.66,P<0.05).Conclusion:The expression of BRMS1 protein in supraglottic cancer is significantly decreased.It had correlation with clinical stage and pathologic differentiation and cervical lymph node metastasis of supraglottic cancer.BRMS1 gene promotor methylation is related with down-expression of BRMS1 gene protein of supraglottic cancer.Maybe BRMS1 gene promotor methylation is one of the reasons of its down-expression.