晚期非小细胞肺癌患者血清细胞因子IL-1β、IL-2R、IL-6及TNF-α水平与厄洛替尼疗效的相关性研究  

Correlation of serum cytokine levels with erlotinib treatment outcome in patients with advanced non-small cell lung cancer

作　　者：刘璐[1,2] 王永生[1,2] 何雅億[1,2] 任胜祥[1,2] 李爱武[1,2] 李雪飞[1,2] 陈晓霞[1,2] 戚川[1,2] 周彩存[1,2] 

机构地区：[1]同济大学附属上海市肺科医院肿瘤科 [2]同济大学医学院肿瘤研究所,上海200433

出　　处：《第三军医大学学报》2012年第20期2056-2059,共4页Journal of Third Military Medical University

摘　　要：目的探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者血清细胞因子水平与厄洛替尼疗效的相关性。方法收集2007年1月至2011年5月同济大学附属上海市肺科医院二线/三线接受厄洛替尼治疗的晚期NSCLC患者162例。收集厄洛替尼治疗前的血样,采用ELISA测定血清中IL-1β、IL-2R、IL-6及TNF-α的表达水平。以细胞因子的中位值为临界值,将细胞因子水平分为高水平组及低水平组。采用Kaplan-Meier生存分析法对入组病例进行生存时间分析,Cox回归多因素分析法对细胞因子水平、病例临床特征与疾病进展时间(time to progression,TTP)及总生存时间(overall survival,OS)进行相关性分析。结果入组病例中位年龄为58岁。其中男性109例,女性53例;吸烟者74例,不吸烟者88例;病理类型为腺癌122例,鳞癌27例,其他类型13例;ECOG PS评分0～1分的病例139例,2～3分23例。在多因素分析结果中,IL-1β、IL-2R和IL-6的表达水平与年龄、性别、ECOG PS评分、吸烟状态、病例类型及肿瘤分期无明显相关性,而TNF-α的表达水平与吸烟状态相关(P=0.045)。生存分析结果显示,IL-6低表达的患者比IL-6高表达的患者有更长的生存期(P<0.01),TNF-α低表达的患者较TNF-α高表达的患者有更长的生存期(P<0.05)。Cox回归多因素分析结果显示,IL-6与TNF-α均为独立的生存相关因子(P<0.01)。结论在二线/三线接受厄洛替尼治疗的晚期NSCLC患者中,IL-6、TNF-α低表达的患者生存期较高表达者长,提示IL-6和TNF-α可能成为厄洛替尼在治疗晚期NSCLC中疗效的预测因子。Objective To investigate the correlation of serum levels of cytokines with clinical outcomes of erlotinib in the second-or third-line therapies to treat the patients with advanced non-small cell lung cancer（NSCLC）.Methods One hundred and sixty-two patients with advanced NSCLC who received erlotinib as either second-or third-line treatment in our department from January 2007 to May 2011 were enrolled in this study.Their median age was 58 years.In this group,109 were male,and 53 were female.Seventy-four were former or current smokers,and 88 were non-smokers.One hundred and twenty-two patients presented with adenocarcinoma,27 had squamous cell carcinoma,and 13 had tumors with other types of histology.Blood samples were collected before the initiation of erlotinib,and the serum levels of IL-1β,IL-2R,IL-6 and TNF-α were assessed by enzyme-linked immunosorbent assay（ELISA）.Cutoff points were defined as the median levels to divided the patients into low and high level groups（IL-1β,26.5 pg/ml;IL-2R,115 pmol/L;IL-6,49.5 pg/ml;TNF-α,48.5 pg/ml）.Kaplan-Meier analysis was performed to estimate the survival time,and Cox regression analyses were employed to correlate cytokines and baseline clinical characteristics with clinical outcomes,including time to progression（TTP） and overall survival（OS）.Results One hundred and thirty-nine patients had an eastern cooperative oncology group（ECOG） performance status of 0 to 1,while the left 23 scored at 2 to 3.Serum levels of IL-1β,IL-2R and IL-6 were not significantly associated with age,gender,ECOG performance status,smoking status,histology,or stage of tumor.But that of TNF-α was associated with smoking status（P =0.045）.Survival analysis showed that patients with low levels of IL-6 had a statistically longer TTP and OS than patients with high expression（P〈0.01）,whereas the subgroup of patients with low levels of TNF-α also demonstrated statistically better TTP and OS than the high level group（P〈0.01）.Cox regression multivariate analysis i

关 键 词：非小细胞肺癌 细胞因子 厄洛替尼 

分 类 号：R181.32[医药卫生—流行病学] R734.2[医药卫生—公共卫生与预防医学]