目的 检测非小细胞肺癌(NSCLC)患者血浆外泌体程序性死亡受体配体1(PD-L1)和表皮生长因子受体(EGFR)的表达，并分析二者与临床特征及预后的相关性。方法 回顾性选取2015年1月至2016年3月在延安大学附属医院就诊的NSCLC患者312例作为研究对象，男178例，女134例;年龄≥55岁180例，＜55岁132例;肿瘤长径≥5 cm 169例，＜5 cm 143例。采用蛋白质免疫印迹技术检测外泌体标志性蛋白CD63、CD81、TSG101的表达情况;采用酶联免疫吸附法(ELISA)检测患者血浆外泌体PD-L1和EGFR水平;采用Kaplan-Meier生存曲线进行预后分析;采用COX回归分析法分析影响NSCLC患者预后的因素;采用x2检验。结果 分化程度低、有淋巴结转移及吸烟史患者血浆外泌体PD-L1和EGFR水平较高(均P＜0。05);患者血浆外泌体PD-L1高水平与EGFR高水平关系密切(P＜0。05)。312例患者中失访27例，随访率为91。35％(285/312);285例随访患者5年生存率为62。46％(178/285)。PD-L1高水平患者的生存率为30。77％(48/156)，PD-L1低水平患者的生存率为83。33％(130/156)，差异有统计学意义(log-rank x2=92。743，P＜0。05)。EGFR高水平患者的生存率为20。51％(32/156)，EGFR低水平患者的生存率为93。59％(146/156)，差异有统计学意义(log-rank x2=119。215，P＜0。05)。多因素分析显示，血浆外泌体PD-L1和EGFR高水平表达、分化程度低、淋巴结转移是影响NSCLC患者预后的独立危险因素(均P＜0。05)。结论 血浆外泌体PD-L1和EGFR表达与NSCLC疾病进展密切相关，可作为患者预后的预测指标。
Correlations between the expressions of PD-L1 and EGFR in the plasma exosomes and clinical features and prognosis in patients with non-small cell lung cancer
Objective To detect the expressions of programmed death ligand 1(PD-L1)and epidermal growth factor receptor(EGFR)in the plasma exosomes in patients with non-small cell lung cancer(NSCLC),and analyze their correlations with clinical features and prognosis.Methods A total of 312 NSCLC patients treated in Yan'an University Affiliated Hospital from January 2015 to March 2016 were retrospectively selected as the research objects.There were 178 males and 134 females,≥55 years old in 180 cases and＜55 years old in 132 cases,tumor length ≥5 cm in 169 cases and＜5 cm in 143 cases.The expressions of exosomal marker proteins CD63,CD81,and TSG101 were detected by Western blot technique,and the expressions of PD-L1 and EGFR in the plasma exosomes were detected by enzyme-linked immunosorbent assay(ELISA).Kaplan-Meier survival curve was used for prognostic analysis.The factors influencing the prognosis of NSCLC patients were analyzed by COX regression analysis.x2 test was used.Results The PD-L1 and EGFR levels in the plasma exosomes were higher in patients with lower degree of differentiation,lymph node metastasis,and smoking history(all P＜0.05).High level of PD-L1 in the plasma exosomes was closely related to high level of EGFR(P＜0.05).Among the 312 patients,27 patients were lost to follow-up,with a follow-up rate of 91.35％(285/312).The 5-year survival rate of the 285 patients was 62.46％(178/285).The survival rate of the patients with high level of PD-L1 was 30.77％(48/156),and that of the patients with low level of PD-L1 was 83.33％(130/156),with a statistically significant difference(log-rank x2=92.743,P＜0.05).The survival rate of the patients with high EGFR level was 20.51％(32/156),and that of the patients with low EGFR level was 93.59％(146/156),with a statistically significant difference(log-rank x2=119.215,P＜0.05).Multifactor analysis showed that high levels of plasma exosome PD-L1 and EGFR expression,lower degree of differentiation,and lymph node metastasis were independent risk factors affecting the prognosis in NSCLC patients(all P＜0.05).Conclusion Plasma exosomal PD-L1 and EGFR expressions are closely associated with disease progression of NSCLC,and can be used as predictors of prognosis.
Non-small cell lung cancerProgrammed death ligand 1Epidermal growth factor receptorExosomesExpression
万方数据
维普
