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目的检测肺癌中经典Wnt信号途径相关基因(WIF-1,sFRP-1,DKK-3)启动子的甲基化状态及β-连环蛋白(β-catenin)的表达情况,探讨其在肺癌发病中的作用。方法应用巢式甲基化特异性聚合酶链反应(nMSP),检测66例肺癌组织、25例相应的癌旁组织和10例正常肺组织以及肺腺癌A549细胞株中WIF-1,sFRP-1和DKK-3基因启动子区域的甲基化;免疫组化SP法检测β-catenin的表达情况。结果正常肺组织均未检测到所选基因的甲基化,肿瘤组织和癌旁组织中WIF-1,sFRP-1,DKK-3基因启动子甲基化的发生率分别为:50·0%vs24·0%(P<0·05),36·4%vs12·0%(P<0·05)和36·4%vs8·0%(P<0·01);重度吸烟患者肿瘤组织3个基因的甲基化发生率明显增高(P<0·05)。肺腺癌A549细胞株中WIF-1和DKK-3基因呈甲基化状态,而sFRP-1基因呈未甲基化状态。免疫组织化学显示肺癌组织中β-catenin的阳性表达率为81·2%,异常表达率为64·4%,且与组织学类型无关(P>0·05)。结论经典Wnt信号途径相关基因启动子甲基化可能与吸烟引起的肺癌有关,甲基化的WIF-1,sFRP-1和DKK-3基因可能成为肺癌表观遗传干预治疗的新靶点。
Objective To detect the methylation status and β-catenin expression of Wnt-1, sFRP-1 and DKK-3 genes in lung cancer and to investigate their roles in the pathogenesis of lung cancer Role. Methods The expression of WIF-1, sFRP-1 and p53 in lung cancer tissues of 66 cases of lung cancer, 25 cases of paracancerous tissues and 10 cases of normal lung tissues and lung adenocarcinoma A549 cells were detected by nested methylation-specific polymerase chain reaction (nMSP) 1 and DKK-3 gene promoter region of the methylation; immunohistochemical SP method to detect the expression of β-catenin. Results Methylation of the selected genes was not detected in normal lung tissues. The rates of methylation of WIF-1, sFRP-1 and DKK-3 genes in tumor tissues and adjacent tissues were 50.0% vs24.0% (P <0.05), 36.4% vs12.0% (P <0.05), and 36.4% vs8.0% (P <0.01), respectively The incidence of methylation of these genes was significantly higher (P <0.05). A549 lung cancer cell line WIF-1 and DKK-3 gene methylation status, and sFRP-1 gene was unmethylated status. Immunohistochemistry showed that the positive expression rate of β-catenin in lung cancer was 81.2% and the abnormal expression rate was 64.4%, which was not related to the histological type (P> 0.05). Conclusion Methylation of Wnt signaling pathway related genes may be related to lung cancer caused by smoking. Methylated WIF-1, sFRP-1 and DKK-3 genes may be new targets for epigenetic intervention in lung cancer.