中国癌症杂志 ›› 2017, Vol. 27 ›› Issue (5): 389-395.doi: 10.19401/j.cnki.1007-3639.2017.05.011

• 论著 • 上一篇    下一篇

非小细胞肺癌患者血清TGF-α与EGFR-TKI治疗敏感性和预后的关系

朱文良1,李 靖2,梁新强3,赖 林1,梁艳艳1,陆运鑫1,侯恩存1   

  1. 1. 广西中医药大学附属瑞康医院肿瘤内科二病区,广西 南宁 530011 ;
    2. 郑州大学附属肿瘤医院微创介入科,河南 郑州 450008 ;
    3. 广西医科大学附属肿瘤医院基础实验部,广西 南宁 530021
  • 出版日期:2017-05-30 发布日期:2017-06-14
  • 通信作者: 朱文良 E-mail:zhuwenlianggz@163.com

The association between plasma TGF-α levels and EGFR-TKI treatment sensitivity and prognosis in NSCLC patients with EGFR mutation

ZHU Wenliang1, LI Jing2, LIANG Xinqiang3, LAI Lin1, LIANG Yanyan1, LU Yunxin1, HOU Encun1   

  1. 1. Department of Medical Oncology, the Second Ward, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China; 2. Department of Minimally-invasive Interventional Radiology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan Province, China; 3. Basic Experiment Department, Guangxi Medical University Affiliated Tumor Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Published:2017-05-30 Online:2017-06-14
  • Contact: ZHU Wenliang E-mail: zhuwenlianggz@163.com

摘要: 背景与目的:表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitor,EGFR-TKI)是EGFR阳性突变非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的优势治疗方案,但其疗效存在较大个体差异。该研究将探讨血清中EGFR的配体转化生长因子(transforming growth factorα,TGF-α)水平是否可作为EGFR基因突变阳性NSCLC患者EGFR-TKI疗效的预测指标,并探讨TGF-α水平与患者预后的关系。方法:收集2012年5月—2014年7月就诊于广西中医药大学附属瑞康医院肿瘤内科门诊及住院部EGFR阳性突变的NSCLC患者75例。在行EGFR-TKI治疗周期前,利用酶联免疫吸附反应(enzyme linked immunosorbent assay,ELISA)检测试剂盒检测各入选患者血清中TGF-α的水平。治疗2个月后行影像学检查,评定治疗效果。探讨TGF-α水平与治疗效果的关系及其预测效能,进一步分析其与患者总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)的关系。结果:75例EGFR阳性突变NSCLC患者经EGFR-TKI治疗后,病情部分缓解(partial response,PR)20例,稳定(stable disease,SD)25例,进展(progression disease,PD)30例,疾病控制(disease control,DC)率达到60%(45例)。PD组患者治疗前血清TGF-α水平高于DC组,差异有统计学意义(P<0.01)。多因素COX回归显示,患者吸烟状态、淋巴结转移程度及TGF-α水平是预后的独立影响因素。ROC分析显示,血清TGF-α水平对患者EGFR-TKI疗效具有良好的预测效能[曲线下面积(area under the curve,AUC)=0.926]且16.75 pg/mL为TGF-α的最佳分界点浓度。血清高浓度TGF-α(≥16.75 pg/mL)与患者吸烟史比例、临床分期、淋巴结转移及治疗效果有关(P<0.05)。TGF-α高浓度较低浓度组患者的OS和PFS中位生存时间缩短,差异有统计学意义(log-rank P<0.05)。结论:高水平血清TGF-α(≥16.75 pg/mL)对NSCLC患者EGFR-TKI治疗抵抗和不良预后有指示作用。

关键词: 转化生长因子, 表皮生长因子受体酪氨酸激酶抑制剂, 非小细胞肺癌, 预后

Abstract: Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment efficiency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction efficiency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-α than patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction efficiency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.

Key words: Transforming growth factor α, Epidermal growth factor receptor-tyrosine kinase inhibitor, Nonsmall cell lung cancer, Prognosis