晚期非小细胞肺癌循环肿瘤细胞EGFR表达与细胞免疫的相关性研究

Correlation between circulating tumor cells EGFR expression and immune function of tyrosine kinase inhibitor treatment in elderly patients with advanced non-small cell lung cancer

目的探讨晚期非小细胞肺癌患者循环肿瘤细胞EGFR的表达与细胞免疫功能的相关性。方法晚期非小细胞肺癌患者均予EGFR-TKI类药物治疗,研究治疗前后循环肿瘤细胞EGFR的表达与细胞免疫功能的相关性。结果 EGFR高表达组CD3+、CD4+、CD4+/CD8+低于低表达组,CD8+高于低表达组,细胞免疫功能低于CTC低表达组(P<0.01)。治疗前后循环肿瘤细胞EGFR低表达组T细胞亚群及NK细胞变化无统计学意义(P>0.05);EGFR高表达组治疗后CD4+/CD8+、NK升高,免疫功能有所恢复(P<0.05)。CD4+/CD8+低表达组和高表达组的中位OS分别为25个月和13个月,1年生存率分别为75.0%和52.4%;2年生存率分别为54.2%和28.6%;3年生存率分别为20.8%和7.1%,两组差异均有统计学意义(P=0.025)。NK高表达组和低表达组的中位OS分别为25个月和12个月,1年生存率分别为77.8%和40.0%;2年生存率分别为55.6%和16.7%;3年生存率分别为22.2%和0.0%,两组差异亦均有统计学意义(P=0.000)。结论循环肿瘤细胞EGFR水平与患者细胞免疫功能呈负相关,EGFR高表达者TKI治疗后免疫功能有所恢复,CD4+/CD8+、NK水平可以作为晚期老年非小细胞肺癌患的EGFR-TKI治疗预后的预测指标。

Objective To find the relationship between circulating tumor cells （CTC） EGFR expression and immune function in patients with advanced non-small cell lung cancer （NSCLC） by tyrosine kinase inhibitor （TKI） treatment. Methods Advanced NSCLC patients treated with TKI were enrolled. CTC, T cell subset and NK ceils in periphery blood were measured before and after treatment. Patients were divided into high EGFR expression （high group） and low EGFR expression （low group）. Correlation among EGFR, T cell subsets, NK cells and patient prognosis were analyzed. Results The amounts o5 CD3＋ , CD4＋ and CD4＋/CD8＋ in high groug were lower than that in low group, but CD8＋ cells in high group were higher than that in the low group （P〈0.01）. T cell subsets and NK ceils were not different before or after treatment in high EGFR group. In the high group after treatment, CD4＋/CD8＋ and NK expression decreased （P〈0.05）, and immune function was enhanced compared with immune function before treatment. The median overall survival was 25 and 13 months in the CD4＋/CD8＋ low and high expression groups, respectively. 1-year survival was 75.0% and 52.4%, 2-year survival was 54.2% and 28.6%, and 3-year survival was 20.8% and 7.1% in the CD4＋/CD8＋ low and high expression groups, respectively and these differences were statistically significant （P = 0. 025）. Median overall survival was 25 and 12 months in the NK high and low expression groups, respectively. The oneyear survival was 77.8% and 40.0%, 2-year survival was 55.6% and 16.7%, and 3-year survival was 22.2% and 0.0% in NK high and low expression groups, respectively and these differences were statistically significant （P= 0. 000）. Conclusion Circulating tumor cells （CTC） EGFR expression were negatively correlated with cellular immune function and immune recovery after EGFR-TKI treatment. CD4＋/ CD8＋ ratio and NK cells may be useful prognostic predictors for advanced NSCLC patients.