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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 expression and methylation status of Fibulin3 gene in non-small cell lung cancer (NSCLC) and to analyze the clinicopathological significance. Methods: Fifty-nine NSCLC patients were collected and pathological paraffin sections were collected for immunohistochemical staining. The DNA of cancer tissue and corresponding paracancerous tissues was extracted. Methylation-specific polymerase chain reaction (MSP) was used to detect methylation of Fibulin3 gene promoter Happening. Results: In 59 NSCLC specimens, the expression of Fibulin3 in 25 cases (42.4%) was lower than that in the corresponding paracancerous tissues (P <0.05). Methylation of Fibulin3 gene in 22 cases and 5 cases of cancer tissues and corresponding paracancerous tissues was detected (P <0.001). The methylation of Fibulin3 promoter resulted in the down-regulation or loss of protein expression (P <0.001), and was positively correlated with clinical stage (P = 0.035) and lymph node metastasis (P = 0.011). CONCLUSION: Inactivation of Fibulin3 gene caused by promoter methylation plays an important role in the development of NSCLC. Methylation of Fibulin3 promoter may be a potential marker for early diagnosis and prognosis evaluation of NSCLC.