microRNA 130b的表达对靶向治疗肺腺癌患者预后的影响

目的探讨microRNA 130b(miR 130b)表达与经靶向治疗的肺腺癌患者预后的关系。方法收集2013年1月至2014年1月间于大连大学附属新华医院胸外科行靶向治疗的肺腺癌患者278例,其中男113例,女165例;年龄40～82(608±103)岁。有肺癌家族史者41例,吸烟史者71例。TNM Ⅲ期者115例,Ⅳ期者163例。靶向治疗前4 h内抽取空腹静脉血,采用定量实时聚合酶链反应(qRT PCR)检测miR 130b的表达,并随访其生存情况。采用Kaplan Meier并Log rank检验对经靶向治疗肺腺癌患者的生存情况进行单因素分析,采用多因素Cox回归模型分析经靶向治疗肺腺癌患者死亡的危险因素。结果278例患者靶向治疗前miR 130b表达水平为113±21,治疗后miR 130b表达水平为93±18,差异有统计学意义(t=10388, P<0001)。miR 130b预测靶向治疗肺腺癌患者死亡的最佳临界点为993;灵敏度为822％,特异度为662％;ROC曲线下面积(AUC)为076。将患者分为miR 130b高表达组(miR 130b≥993,145例)和低表达组(miR 130b<993,114例),miR 130b高表达组有肿瘤家族史、吸烟、低肿瘤分化程度以及高TNM分期患者比例高于低表达组。本组259例患者获得随访,中位随访时间为42个月,死亡191例。miR 130b高表达组、低表达组患者中位生存时间分别为36和48个月,miR 130b低表达组患者的生存情况优于高表达组(Log rank χ2=28341,P<0001)。多因素Cox回归分析显示,肺癌家族史、吸烟史、较低分化程度、较高TNM分期、miR 130b高表达是经靶向治疗肺腺癌患者死亡的独立危险因素。结论miR 130b表达上调的肺腺癌患者靶向治疗预后更差,其可能作为肺腺癌患者靶向治疗预后的生物标志物之一。

Effects of microRNA-130b expression on the efficacy of targeted therapy for lung cancer patients

Objective To investigate the relationship between the expression of MicroRNA-130b and the therapeutic effect of targeted therapy for lung adenocarcinoma. Methods Two hundred and seventy eight lung adenocarcinoma patients who underwent target therapy treatment in our hospital from January 2013 to January 2014 were included. There were 113 males and 165 females among the 278 patients. The average age was (60.8 ±10.3) years (range: 40-82 years). There were 41 patients having a family history of lung cancer, 71 patients having a history of smoking. According to TNM stage, 78 patients were classified into stage I, 40 patients were classified into stage II, 109 patients were classified into stage III, and 51 patients were classified into stage IV. Preoperative fasting venous blood samples were collected to measure the expression of MicroRNA-130b, and their survival status were followed up. Kaplan-meier with log-rank test were used for univariate analysis, and significant factors in univariate analysis were introduced into Cox regression model. Results The expression level of MicroRNA-130b was 11.3±2.1. At the end of January 2019, 19 out of 278 patients were lost to follow-up, with a follow-up rate of 93.17%. Of the 259 patients who have been followed up, 191 patients died. Kaplan-Meier with Log-rank test showed that family history of lung cancer HR (95% CI): 1.17（1.03-1.28）], smoking history HR (95% CI): 2.25（2.18-3.24）], lower differentiation HR (95% CI): 1.62（1.51-2.27）], higher TNM stages HR (95% CI): 2.04（1.85-2.03）], higher expression of MicroRNA-130b HR (95% CI): 2.77（2.13-3.57）] increased the risk of mortality in lung adenocarcinoma patients treated with targeted therapy. Multivariable COX regression analysis showed that family history of lung cancer HR (95%CI): 1.15（1.06-1.19）], smoking history HR (95%CI): 2.21（2.13-3.17）], lower differentiation HR (95%CI: 1.59（1.52-2.03）], higher TNM stage HR (95%CI): 1.97（1.87-2.02）], higher MicroRNA-130b expression HR (95%CI): 2.64（2.23-3.62）] were independent risk factors for mortality of lung adenocarcinoma patients treated with targeted therapy. Conclusion The expression of MicroRNA-130b is an independent risk factor for mortality of lung adenocarcinoma patients treated with target therapy. Patients with higher expression of MicroRNA-130b had higher risk of death.