microRNA-130b的表达对靶向治疗肺腺癌患者预后的影响

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

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。TNMⅢ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-rankχ^2=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。

Objective To investigate the relationship between the expression of microRNA-130b(miR-130b)and the prognosis of targeted therapy for lung adenocarcinoma.Methods Two hundred and seventy eight lung adenocarcinoma patients who underwent target therapy treatment in Department of Thoracic Surgery,the Xinhua Hospital Affiliated to Dalian University from January 2013 to January 2014 were included.There were 113 males and 165 females among the 278 patients,age from 40 to 82 with the average age of(60.8±10.3)years old.41 patients had a family history of lung cancer,and 71 patients had a history of smoking.According to TNM stage,115 patients were classified into stage III,and 163 patients were classified into stage IV.Preoperative fasting venous blood samples were collected to measure the expression of miR-130b by quantitative real-time polymerase chain reaction(qRT-PCR),and their survival status were followed up.Kaplan-Meier with Log-rank test were used for univariate analysis,and multivariable Cox regression model were used for analysis of risk factors for targeted treatment of patients with lung adenocarcinoma.Results The expression level of miR-130b of the 278 patients were11.3±2.1 and 9.3±1.8 for before and after targeted therapy,respectively(t=10.388,P<0.001).The optimal cut-off point for miR-130b predictive death in patients with lung adenocarcinoma was 9.93 with the sensitivity of 82.2%,specificity of 66.2%and AUC of 0.76.The patients were divided into miR-130b high expression group(miR-130b≥9.93,114 cases)and low expression group(miR-130b<9.93,105 cases).The miR-130b high expression group had a higher proportion of family history of tumor,smoking,and low tumor,lower differentiation,and high TNM staging were higher than those in the low expression group.Two hundred and fifty nine patients completed followed up with a median follow-up of 42 months and 191 deaths.The median survival time of patients in miR-130b high expression group and low expression group was 36 and 48 months,respectively.The survival of patients with low expression of miR-130b was better than that of high expression group(Log-rankχ^2=28.341,P<0.001).Multivariate Cox regression analysis showed that family history of lung cancer,smoking history,lower differentiation,higher TNM stage,and high expression of miR-130b were independent risk factors for targeted treatment of patients with lung adenocarcinoma.Conclusions The prognosis of targeted therapy for lung adenocarcinoma patients with up-regulated miR-130b expression is worse,which may be one of the biomarkers for the prognosis of targeted therapy in patients with lung adenocarcinoma.