喉鳞状细胞癌组织中NDRG1、NDRG2基因启动子区CpG岛甲基化状态及其蛋白的表达

发布时间：2018-05-15 19:39

本文选题：喉癌 + NDRG　；参考：《中国肿瘤生物治疗杂志》2014年06期

【摘要】：目的:探讨喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)组织中N-myc下游调节基因1(N-myc downstream regulated gene 1,NDRG1)及NDRG2基因启动子甲基化状态和蛋白表达情况及其临床意义。方法:应用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)技术及免疫组织化学(immunohistochemestry,IHC)法检测45例LSCC组织、18例癌旁组织中NDRG1、NDRG2基因启动子区Cp G岛甲基化及蛋白表达情况,分析其与临床特征的关系。结果:LSCC组织中NDRG1及NDRG2基因启动子区的甲基化发生率显著高于癌旁正常组织[66.7%(30/45)vs 33.3%(6/18),53.3%(24/45)vs 22.2%(4/18),均P0.05],其高甲基化与淋巴结转移及临床分期有关(P0.05),与病理分级、临床分型、吸烟史、年龄和性别无关(P0.05)。在LSCC组织中,NDRG1及NDRG2蛋白的阳性表达率显著低于癌旁组织[37.8%(17/45)vs 88.9%(16/18),33.3%(15/45)vs 83.3%(15/18),均P0.01],其低蛋白表达与淋巴结转移及临床分期有关(P0.05),与病理分级、临床分型、吸烟史、年龄和性别无关(P0.05)。LSCC组织中NDRG1及NDRG2启动子区甲基化与其蛋白表达呈负相关(r1=-0.713,P0.01;r2=-0.472,P0.01)。结论:在LSCC组织中NDRG1及NDRG2基因均呈高甲基化及低蛋白表达状态,这可能与喉癌的发生和发展有关,NDRG1及NDRG2基因启动子区Cp G岛的异常甲基化可能是抑制它们蛋白表达的机制之一。
[Abstract]:Objective: to investigate the methylation status and protein expression of N-myc downstream regulatory gene 1(N-myc downstream regulated gene 1 and NDRG2 gene promoter and its clinical significance in laryngeal squamous cell carcinoma (LSCC). Methods: methylation and protein expression of CP G island in the promoter region of NDRG1 and NDRG2 gene were detected by methylation specific PCR(methylation specific polymerase chain reaction- mSPand immunohistochemical histochemistry-IHC assay in 18 paracancerous tissues of 45 cases of LSCC, and the relationship between methylation and clinical features was analyzed. Results the incidence of methylation in the promoter region of NDRG1 and NDRG2 gene was significantly higher in the tissues of NDRG1 and NDRG2 than in the normal tissues adjacent to cancer. [66.7%(30/45)vs 33.3R / 618 / 53.35 / 45 vs 22.2P / 18, respectively, P0.05], its hypermethylation was related to lymph node metastasis and clinical stage (P0.05), and to pathological grade, clinical classification, smoking history. Age was not related to sex (P 0.05). The positive expression rate of NDRG2 protein in LSCC tissues was significantly lower than that in adjacent tissues [37.8%(17/45)vs 88.9%, 16 / 18 / 33. 3 / 45% vs 83.3% / 18%, all P 0.01]. The low protein expression was related to lymph node metastasis and clinical stage (P 0.05), and to pathological grade, clinical classification, smoking history. The methylation of NDRG1 and NDRG2 promoter was negatively correlated with the protein expression of P0.05. LSCC. There was a negative correlation between methylation of NDRG1 and NDRG2 promoter and its protein expression. Conclusion: both NDRG1 and NDRG2 genes present hypermethylation and low protein expression in LSCC tissues, which may be related to the occurrence and development of laryngeal carcinoma and the abnormal methylation of CP G islands in the promoter region of NDRG2 gene, which may be one of the mechanisms that inhibit their protein expression.
【作者单位】：河北医科大学第四医院耳鼻咽喉头颈外科;
【分类号】：R739.65

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