Fibulin3基因在非小细胞肺癌中的蛋白表达及甲基化检测

Analysis of Fibulin3 protein expression and promoter methylation status in non-small cell lung cancer

目的:检测Fibulin3基因在非小细胞肺癌患者(non-small cell lung cancer,NSCLC)组织中的表达和甲基化状态,并分析其临床病理意义。方法:收集59例NSCLC患者术后病理蜡块,进行免疫组化染色;提取癌组织及相应癌旁组织DNA,甲基化特异性聚合酶链反应(MSP)检测Fibulin3基因启动子区甲基化情况。结果:59例NSCLC标本中,25例(42.4%)Fibulin3表达水平比相应癌旁组织下调(P<0.05);癌组织和相应癌旁组织甲基化22例和5例检出Fibulin3基因启动子区高甲基化,其阳性率分别为37.3%和8.5%,差异具有统计学意义(P<0.001);Fibulin3启动子甲基化导致蛋白表达下调或缺失(P<0.001),并与临床分期(P=0.035)及淋巴结转移(P=0.011)相关。结论:启动子甲基化引起的Fibulin3基因失活在NSCLC发生发展中起重要作用,Fibulin3启动子甲基化可能成为NSCLC早期诊断和预后评估的潜在标记物。

Objective：To detect the protein expression and promoter methylation status of Fibulin3 gene in tissue of non-small cell lung cancer （NSCLC） patients and evaluate its correlation with clinicopathological features. Methods： A total of 59 paired NSCLC specimens and their adjacent normal tissues were collected in the study, protein expression was analyzed by immunohistochemical staining, promoter methylation status of Fibulin3 gene was determined by methylation-specific polymerase chain reaction （MSP）. Results： Silence or down-regulation of Fibulin3 expression was observed in 25 of 59 （32.1%） NSCLC tissues, as compared with the adjacent normal tissues （P〈0.05）, the frequency of promoter methylation in tumor and non-tumor tissue was 37.3% and 8.5%, respectively, the difference was statistically significant （P〈0.001）; Fibulin3 hypermethylation was correlated with loss of protein expression （P〈0.001）, advanced clinic stage （P=0.035） and lymph metastasis （P=0.011）. Conclutions： Frequent inactivation of Fibulin3 by promoter methylation plays an important role in NSCLC initiation and progression, detection of Fibulin3 methylation may be a promising biomarker for the early diagnosis and prognosis assessment of NSLCL.