晚期非小细胞肺癌恶性胸腔积液IL-6水平与EGFR-TKIs治疗疗效及预后的关系  

Pleural IL-6 level predicts clinical outcomes in patients with advanced non-small cell lung cancer receiving EGFR-TKIs

作　　者：袁琪[1] 王伟[1] 徐春华[1] YUAN Qi;WANG Wei;XU Chunhua(Department of Respiratory Medicine,Nanjing Chest Hospital(Affiliated Nanjing Brain Hospital,Nanjing Medical University),Jiangsu Nanjing 210000,China)

机构地区：[1]南京市胸科医院(南京医科大学附属脑科医院)呼吸内科,江苏南京210000

出　　处：《现代肿瘤医学》2022年第7期1224-1228,共5页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81700068)。

摘　　要：目的:探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)恶性胸腔积液中白介素-6(interleukin-6,IL-6)与接受表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)治疗的疗效和预后的关系。方法:回顾性分析2014年01月至2017年05月在我院呼吸内科病理确诊NSCLC恶性胸腔积液73例患者的临床资料,采用流式荧光法检测胸腔积液中IL-6水平,蛋白磷酸化流式分析技术检测外周血单个核细胞中pSTAT1和pSTAT3表达,通过Kaplan-Meier法构建生存曲线,Cox比例风险模型行多因素分析。结果:整体入组患者的客观缓解率为64.4%,高IL-6组17例客观缓解率为41.2%,低IL-6组56例客观缓解率为71.5%,低IL-6组客观缓解率优于高IL-6组(P=0.006),所有完全缓解患者均为低IL-6组。高IL-6组和低IL-6组治疗失败时间(time to treatment failure,TTF)和总生存期(overall survival,OS)比较结果分别为:6.8个月vs 10.5个月(P<0.0001),20.5个月vs 26.4个月(P=0.0003)。多因素回归分析示IL-6水平是影响TTF(P<0.001,OR 6.190,95%CI 3.136~12.221)和OS(P<0.001,OR 6.28895%CI 3.060~12.925)的预后因素。在CD4+T淋巴细胞中,高IL-6组pSTAT1表达低于低IL-6组(P<0.001),两组间pSTAT3表达均无明显差异。结论:恶性胸腔积液中IL-6水平可能是预测EGFR敏感突变型NSCLC接受EGFR-TKIs治疗的患者临床预后的有效指标。Objective:To investigate the relationship between the level of interleukin-6(IL-6)in malignant pleural effusion and the efficacy and prognosis of the(EGFR)-sensitive mutant advanced non-small cell lung cancer(NSCLC)receiving growth factor receptor-styrosine kinase inhibitors(EGFR-TKIs).Methods:Retrospectively,we analyzed the clinical data of 73 patients with malignant pleural effusion diagnosed with advanced NSCLC in the department of respiratory medicine in hospital from January 2014 to May 2017.Flow fluorescence assay was used to detect IL-6 in pleural effusion.Phosphorylated-protein flow cytometry(PhosFlow)assay was used to measure changes in phosphorylated STAT1 and STAT3 upon peripheral blood mononuclear cells.The Kaplan-Meier method was used to construct a survival curve,and the Cox proportional hazards model was used for multivariate prognostic analysis.Results:The objective response rate of the overall enrolled patients was 64.4%,the objective response rate(ORR)of 17 patients with the high IL-6 level was 41.2%,the ORR of 56 patients with the low IL-6 level was 71.5%,and the ORR of the low IL-6 group was higher than the high IL-6 group(P=0.006).All patients with complete response were in low IL-6 group.The results of time to treatment failure(TTF)and overall survival(OS)in the high IL-6 group and the low IL-6 group were:6.8 months vs 10.5 months(P<0.0001),20.5 months vs 26.4 months(P=0.0003),respectively.Multivariate regression analysis showed that IL-6 level was a prognostic factor affecting TTF(P<0.001,OR 6.190,95%CI 3.136~12.221)and OS(P<0.001,OR 6.28895%CI 3.060~12.925).Patients with high levels of pleural IL-6 produced a significantly lower pSTAT1 response than those with low levels,in CD4+T cells(P<0.001),no significant differences in pSTAT3 were observed between the two groups.Conclusion:The level of IL-6 in malignant pleural effusion may be an effective indicator to predict the prognosis of EGFR-sensitive mutant NSCLC receiving EGFR-TKIs.

关 键 词：恶性胸腔积液 晚期非小细胞肺癌 白介素-6 EGFR-TKIS 

分 类 号：R734.2[医药卫生—肿瘤]