EPHB6受体型酪氨酸蛋白激酶在非小细胞肺癌中高甲基化失活

EPHB6 receptor tyrosine kinase is inactive of hypermethylation in non-small cell lung cancer

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者促红细胞生成素产生肝细胞B6(erythropoietin-pro-ducing hepatocyte B6,EPHB6)受体酪氨酸激酶表达与癌细胞的远处转移的关系,及其EPHB6表达失活的机制。方法测定正常肺组织(n=9)、未发生转移的NSCLC肿瘤组织(n=39)和发生转移的NSCLC肿瘤组织(n=39)中EPHB6的表达水平。检测24例NSCLC患者的正常肺组织和肿瘤组织中EPHB6的表达水平,并比较分析EPHB6甲基化水平与其mRNA表达水平的相关性。结果与正常的肺组织相比,NSCLC中EPHB6的mRNA和蛋白水平均显著降低,降低的EPHB6表达水平与NSCLC患者转移的危险性增加有关。EPHB6的表达失活与高甲基化有关,在非小细胞系中EPHB6的表达可以被5-氮-2'-脱氧胞苷激活。结论 NSCLC中EPHB6表达沉默的机制是启动子区的高甲基化。

Objective To explore the relationship of erythropoietin-producing hepatocyte B6（EPHB6） receptor tyrosine kinase expression with the distant metastasis of cancer cell in early stage non-small cell lung cancer（NSCLC） patients,and the mechanism of inactivation of EPHB6 expression.Methods The expression levels of EPHB6 were compared among normal lung tissue（n=9）,NSCLC without metastasis（n=39）,and NSCLC with metastasis（n=39）.EPHB6 expression levels in matched tumor-normal pairs from 24 NSCLC patients were analyzed.Correlation of EPHB6 methylation levels with EPHB6 mRNA expression was analyzed.Results Compared with matched normal lung tissue,mRNA and protein expression levels of EPHB6 were both significantly reduced in NSCLC.Decreased EPHB6 expression level was associated with an increased risk of metastasis in NSCLC patients.Loss of EPHB6 expression was correlated with hypermethylation.EPHB6 expression was induced by 5-Aza-2′-deoxycytidine treatment in a NSCLC cell line.Conclusion The results demonstrate that EPHB6 is frequently silenced by hypermethylation of its promoter in NSCLC.