Huang Chun-Yao, Hsieh Ming-Ju, Wu Wen-Jun, Chiang Whei-Ling, Liu Tu-Chen, Yang Shun-Fa, Tsao Thomas Chang-Yao
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Pulmonary Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan.
J Cancer. 2018 Jun 15;9(14):2518-2524. doi: 10.7150/jca.25824. eCollection 2018.
EGFR mutation of Non-small cell lung cancers (NSCLC) was predominantly seen in Asian population and it was considered as a predictor of responsiveness. Eendothelial nitric oxide synthase (eNOS) plays a vital role in chronic inflammation and carcinogenesis. In this study, we aimed to explore the association between the genetic polymorphisms of (-786T/C and 894 G/T) and EGFR mutation in patients with lung adenocarcinoma. A total of 277 patients with diagnosed lung adenocarcinoma were recruited between years 2012 and 2015. All study subjects underwent the analysis of genetic variants (-786 T/C and 894 G/T) using real-time polymerase chain reaction (PCR) genotyping. Our results showed that, among the 277 patients, variant types (GT + TT) of 894 G/T polymorphism were significantly positively correlated with EGFR mutation type, specifically exon 19 in-frame deletion. With the subgroup of EGFR L858R mutation, variant genotypes (GT + TT) of 894 G/T were significantly associated with lymph node invasion. Moreover, in silico analysis indicated that 894 G/T altered the eNOS expression. In conclusion, our study showed that 894 G/T variants were significantly associated with EGFR mutation types of lung adenocarcinoma, specifically exon 19 in-frame deletion. This may be utilized as a prediction of tumor invasiveness and therapy responsiveness.
非小细胞肺癌(NSCLC)的表皮生长因子受体(EGFR)突变主要见于亚洲人群,被视为反应性的预测指标。内皮型一氧化氮合酶(eNOS)在慢性炎症和致癌过程中起重要作用。在本研究中,我们旨在探讨肺癌腺癌患者中(-786T/C和894 G/T)基因多态性与EGFR突变之间的关联。2012年至2015年期间共招募了277例确诊为肺腺癌的患者。所有研究对象均采用实时聚合酶链反应(PCR)基因分型法对基因变异(-786 T/C和894 G/T)进行分析。我们的结果显示,在277例患者中,894 G/T多态性的变异类型(GT + TT)与EGFR突变类型,特别是外显子19框内缺失,显著正相关。在EGFR L858R突变亚组中,894 G/T的变异基因型(GT + TT)与淋巴结侵袭显著相关。此外,计算机模拟分析表明894 G/T改变了eNOS的表达。总之,我们的研究表明,894 G/T变异与肺腺癌的EGFR突变类型显著相关,特别是外显子19框内缺失。这可用于预测肿瘤侵袭性和治疗反应性。