非小细胞肺癌组织中抑癌基因RUNX3启动子甲基化与肿瘤侵袭相关基因E-Cad、MMP-7和TIMP-1蛋白表达的关系

目的:探讨非小细胞肺癌组织中抑癌基因RUNX3启动子甲基化与肿瘤侵袭相关基因E-Cad、MMP-7和TIMP-1蛋白表达的关系。方法:收集并分析我院2017年1月至2018年1月期间收治入院的65例非小细胞肺癌患者组织,采用巢氏甲基化特异性PCR(n MSP)法检测RUNX3启动子甲基化情况;链霉菌素-生物素过氧化物酶(S-P)染色法检测肿瘤侵袭相关基因E-Cad、MMP-7和TIMP-1蛋白表达并计数,并回顾性分析RUNX3启动子甲基化状态与临床病理特征、肿瘤侵袭相关基因表达的关系。结果:65例NSCLC组织样本中有27例出现RUNX3启动子的甲基化(41. 54%)。RUNX3启动子甲基化与病理类型有关,腺癌(81. 48%)高于鳞癌(18. 52%,P=0. 003);且与临床分期有关(P=0. 003),主要分布于Ⅲ期(55. 56%)和Ⅳ期(33. 33%)。S-P染色并计数结果显示,E-Cad、MMP-7和TIMP-1蛋白表达阳性率分别为56. 92%、46. 15%和52. 31%;且在RUNX3基因启动子甲基化组中阳性表达率与非甲基化组中阳性率相比差异均具有统计学意义(P<0. 05)。结论:RUNX3基因启动子的甲基化与NSCLC的侵袭和转移密切相关,有望为NSCLC的临床诊疗提供新的思路。

Relationship between methylation of tumor suppressor gene RUNX3 and expression of E-Cad,MMP-7 and TIMP-1 in tumor invasive non-small cell lung cancer tissues

Objective:To investigate the relationship between the methylation of RUNX3 promoter and the expression of E-Cad,MMP-7 and TIMP-1 in non-small cell lung cancer tissues.Methods:The tissues of 65 patients with non-small cell lung cancer admitted from January 2017 to January 2018 in our hospital were collected and analyzed.The methylation of RUNX3 promoter was detected by nested methylation-specific PCR(nMSP)method.Streptavidin-biotin peroxidase(S-P)staining was used to detect the expression of tumor invasive genes E-Cad,MMP-7 and TIMP-1 and counted.The methylation status of RUNX3 promoter was analyzed retrospectively for the relationship with the pathological characteristics and tumor invasion-related gene expression.Results:The methylation of the RUNX3 promoter occurred in 27 of 65 NSCLC tissue samples(41.54%).RUNX3 promoter methylation was associated with histological type,adenocarcinoma(81.48%)was higher than squamous cell carcinoma(18.52%,P=0.003);RUNX3 promoter methylation was also related to clinical stage(P=0.003),mainly distributed in stage Ⅲ(55.56%)and Ⅳ period(33.33%).S-P staining and counting results showed that the positive rate of E-Cad,MMP-7 and TIMP-1 protein expression were 56.92%,46.15% and 52.31%,respectively;and the positive expression rate in the RUNX3 gene promoter and non-methylation group were statistically different(P<0.05).Conclusion:The methylation of RUNX3 gene promoter is closely related to the invasion and metastasis of NSCLC,and it is expected to provide new ideas for clinical diagnosis and treatment of NSCLC.