肺腺癌患者预后及EGFR基因T790M突变状况的相关因素分析

Analysis of correlation factors of prognosis and EGFR gene T790M mutation in patients with lung adenocarcinoma

目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变肺腺癌患者的预后相关因素以及与靶向治疗后疾病进展患者发生T790M突变相关的因素。方法:收集2015年1月—2018年12月就诊于郑州大学第一附属医院的137例晚期肺腺癌患者的资料。所有患者均携带EGFR基因敏感突变并接受了第一代EGFR-酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)靶向治疗。应用Kaplan-Meier法绘制生存曲线,采用log-rank法进行单因素分析,COX比例风险回归模型进行多因素分析,回顾性分析患者的临床病理特征和血液学指标与预后的关系,以及与靶向治疗后疾病进展患者发生T790M突变相关的因素。结果:截至随访结束,137例患者中有53例(38.7%)患者出现疾病进展,84例(61.3%)患者病情稳定或缓解,全组患者的中位无进展生存期(progression-free survival,PFS)为16.0个月(1.0~51.0个月),平均PFS为9.1个月。单因素生存分析结果显示,治疗前患者的吸烟状况、转移器官个数、Ki-67增殖指数以及γ-谷氨酰胺转移酶(gamma-glutamyl transferase,γ-GGT)的表达水平与PFS相关(P值均<0.05),而吸烟、器官转移个数超过1个、Ki-67增殖指数≥50%以及γ-GGT表达水平≥58 U/L的患者预后不良。多因素生存分析结果显示,转移器官个数、Ki-67增殖指数和γ-GGT表达水平是独立的预后因素。在53例出现疾病进展的患者中,32例患者接受了二次组织活检及基因检测,其中19例(59.4%)患者为T790M突变阳性,13例(40.6%)患者为T790M突变阴性,Fisher确切概率法检测结果显示年龄与T790M突变状态有关(P=0.029)。结论:转移器官个数、Ki-67增殖指数和γ-GGT的表达水平是肺腺癌患者的独立预后因素,可以作为肺癌靶向治疗疗效的预测因素。在接受第一代EGFR-TKIs靶向治疗后出现疾病进展的患者中,年龄<65岁的患者更可能发生T790M突变。

Objective:To explore the prognostic factors of patients with lung adenocarcinoma carrying epidermal growth factor receptor (EGFR) gene mutation,and the factors associated with T790M mutation in patients with disease progression after targeted therapy.Methods:The data of 137 patients with advanced lung adenocarcinoma who visited the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2018 were collected.All patients carried EGFR gene sensitive mutation and received the first generation of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) targeted therapy.Kaplan-Meier method was used to draw survival curve,log-rank method was used for univariate analysis,and the COX proportional hazard regression model was used for multivariate analysis.The association of clinicopathological characteristics and hematological indexes with the prognosis,as well as the factors related to T790M mutation in patients with disease progression after targeted therapy were retrospectively analyzed.Results:By the end of follow-up,53 (38.7%) patients had disease progression,84 (61.3%) patients had stable disease or remission.The median progression-free survival (PFS) was 16.0 months (1.0-51.0 months),and the average PFS was 9.1 months.Univariate survival analysis showed that smoking status before treatment,number of metastatic organs,Ki-67 index,and the expression level of gamma-glutamyl transferase (γ-GGT) were correlated with PFS (all P < 0.05),while the patients with smoking habits,more than one organ metastasis,Ki-67 index ≥ 50% and γ-GGT expression level ≥ 58 U/L had poor prognosis.Multivariate survival analysis showed that the number of metastatic organs,Ki-67 index and γ-GGT expression level were independent prognostic factors.Among the 53 patients with disease progression,32 patients underwent second biopsy and gene detection.Among them,19 patients (59.4%) were positive for T790M mutation,and 13 patients (40.6%) were negative for T790M mutation.Fisher’s exact probability test showed that the age was related to T790M mutation status (P=0.029).Conclusion:The number of metastatic organs,Ki-67 index and γ-GGT expression level are independent prognostic factors for patients with lung adenocarcinoma,and can be used as predictors of the efficacy of targeted therapy for lung cancer.In patients with disease progression after first-generation EGFR-TKIs targeted therapy,who younger than 65 years old are more likely to have T790M mutation.