染色体3p区抑癌基因在非小细胞肺癌中的甲基化状况与临床意义

摘要

Background and objective DNA methylation is one of the mechanisms of epigenetics.Allelic loss located on chromosome 3p happen frequently and early in non-small cell lung cancer (NSCLC).The aim of this study is to detect the promoter methylation status of tumor suppressor genes (TSGs) located on chromosome 3p in NSCLC and to evaluate its correlation with clinicopathological features.Methods A total of 78 paired NSCLC specimens and their adjacent normal tissues were collected in the study Promoter methylation status was determined by methylation-specific polymerase chain reaction (MSP).DLECl gene expression was determined by RT-PCR and immunohistochemistry.Results Aberrant methylation frequency of DLEC1, RASSFIA, hMLHl, RARβ and FHIT genes detected in 78 NSCLC tissues were 41.03％, 39.74％, 30.77％and 16.67％, respectively, which were all significantly higher than that in adjacent normal tissues.However, FHIT gene was not detected methylation in both cancerous and non-cancerous tissues.DLECl hypermethylation was associated with advanced stage (P=0.011) and lymph metastasis (P=0.019), while RASSFIA, RARp, hMLHl and mean methylation index (MI) were not correlated with any clinicopathological parameters.Moreover, DLEC1 gene downregulation was detected in 56.41％ (44/78) NSCLC tissues and correlated with promoter hypermethylation.Conclusion Frequent hypermethylation of TSGs located on chromosome 3p was a common event contributing to NSCLC pathogenesis and DLECl methylation was closely correlated with loss of expression.%背景与目的 DNA甲基化是表观遗传学的一种调控机制,染色体3p区等位基因缺失是肺癌发生中较频繁和早期的事件之一.检测染色体3p区5个典V抑癌基因DLECI、RASSFIA,hMLHI、RAPP和FH1T4非小细胞肺癌(non-small cell lung cancer,NSCLC)中的甲基化状况,分析其临床意义.方法 取78例NSCLC患者术中癌组织及相应正常肺组织标本.采用甲基化特异性聚合酶链反应(methylation specific PCR,MSP)检测基因启动子区甲基化状况,RT-PCR和免疫组化检测DLEC1基因表达.结果 78例NSCLC组织中,DLECI,RASSFIA,RA邢和hMLHI甲基化频率分别为41.03%,39.74%,30.77%和16.67%,与正常组织相比差异均具有统计学意义.FHIT基因在癌组织和正常组织均无甲基化.DLECI甲基化与患者临床分期(P=0.011)和淋巴结转移相关(P=0.019),而RASSFIA,RARβ、hMLHI基因甲基化以及平均甲基化指数与临床病理特征无关联.56.41% ( 44/78)的NSCLC组织中发现DLEC1基因表达下调或缺失,且与启动子甲基化有关.结论 3p区抑痛基因甲基化是NSCLC发生中的重要分子事件,可能作为NSCLC早期诊断的潜在生物标记.新型抑癌基因DLEC1失活与启动子高甲基化有关.