Zhou Xiuzhi, Cai Li, Liu Junjie, Hua Xiaomin, Zhang Ying, Zhao Huilin, Wang Bin, Li Boqing, Gai Pengzhou
Department of Microbiology, Qingdao University, Qingdao, Shandong 266071, P.R. China.
School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Oncol Lett. 2018 Jul;16(1):362-370. doi: 10.3892/ol.2018.8681. Epub 2018 May 9.
Epidermal growth factor receptor (EGFR) is an important gene in the development of lung adenocarcinoma. However, there is controversy regarding the association between EGFR mutations and survival time of patients with lung adenocarcinoma. In the present study, tissue specimens and clinical data were collected from 219 patients with lung adenocarcinoma who had not undergone prior radiotherapy or chemotherapy. EGFR mutations were detected using a fluorescence polymerase chain reaction method, and the association between EGFR mutations and clinicopathological characteristics was analyzed. Overall survival (OS) curves were constructed using the Kaplan-Meier method and the influence of clinicopathological characteristics on OS was analyzed using the Cox regression model. The EGFR mutation rate was 50.7%, and the most common mutations were the L858R substitution mutation in exon 21 (L858R; 54.9%) and the deletion mutation in exon 19 (19-Del; 36%). The presence of EGFR mutations varied significantly with sex, smoking history, T stage, vascular invasion and adenocarcinoma subtypes (P<0.05). The survival time was significantly longer for female, young (<60 years-old), non-smokers or patients exhibiting EGFR mutations (G719X, 19-Del, L858R and L861Q). The survival time was also significantly longer for patients with a 19-Del mutation, early stage tumors, tyrosine kinase inhibitors targeted therapy-treated patients, for those not exhibiting nerve or vascular invasion, and for those without disease recurrence (P<0.05). Multivariate analysis revealed that tumor pathological Tumor-Node-Metastasis (pTNM) stage, nerve invasion, vascular invasion, EGFR mutation and the 19-Del mutation were independent predictors (P<0.05). Therefore, tumor pTNM stage, nerve invasion, vascular invasion and EGFR mutation status, particularly that of 19-Del, were independent prognostic factors for patients with lung adenocarcinoma.
表皮生长因子受体(EGFR)是肺腺癌发生发展中的一个重要基因。然而,关于EGFR突变与肺腺癌患者生存时间之间的关联存在争议。在本研究中,收集了219例未接受过放疗或化疗的肺腺癌患者的组织标本和临床数据。采用荧光聚合酶链反应法检测EGFR突变,并分析EGFR突变与临床病理特征之间的关联。使用Kaplan-Meier法构建总生存(OS)曲线,并使用Cox回归模型分析临床病理特征对OS的影响。EGFR突变率为50.7%,最常见的突变是21外显子的L858R替代突变(L858R;54.9%)和19外显子的缺失突变(19-Del;36%)。EGFR突变的存在在性别、吸烟史、T分期、血管侵犯和腺癌亚型方面存在显著差异(P<0.05)。女性、年轻(<60岁)、不吸烟者或存在EGFR突变(G719X、19-Del、L858R和L861Q)的患者生存时间显著更长。19-Del突变患者、早期肿瘤患者、接受酪氨酸激酶抑制剂靶向治疗的患者、未出现神经或血管侵犯的患者以及无疾病复发的患者生存时间也显著更长(P<0.05)。多因素分析显示,肿瘤病理肿瘤-淋巴结-转移(pTNM)分期、神经侵犯、血管侵犯、EGFR突变和19-Del突变是独立的预测因素(P<0.05)。因此,肿瘤pTNM分期、神经侵犯、血管侵犯和EGFR突变状态,尤其是19-Del突变状态,是肺腺癌患者的独立预后因素。