Zhang L Q, Chen Y, Pan X, Xing Y F, Shi M H, Chen Y J
Department of Respiratory Diseases, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Zhonghua Yi Xue Za Zhi. 2016 Dec 27;96(48):3870-3874. doi: 10.3760/cma.j.issn.0376-2491.2016.48.004.
To analyze the expression of soluble programmed death ligand 1 (sPD-L1) in the serum of patients with advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma and to explore its clinical implications. Seventy-two patients with EGFR mutated advanced lung adenocarcinoma (EGFR mutation group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from May 2015 to July 2016. Thirty-one patients with advanced EGFR wild type (WT) lung adenocarcinoma [EGFR WT group, diagnosed via mini specimens from bronchoscopy or transthoracic needle aspiration biopsy (TNAB), matching in sex, age and tumor stage with EGFR mutation group] were also enrolled as controls. The sPD-L1 protein expression in serum was determined by enzyme-linked immunosorbent assay (ELISA) kit. According to the clinical response of two-month EGFR-tyrosine kinase inhibitor (TKI) treatment, all patients were divided into two groups: 36 cases in disease progression groups (PD group) and 36 cases in disease control group (DC group). The sPD-L1 level in peripheral blood between the two groups was analyzed. In EGFR mutation group, the relationship of serum sPD-L1 with TNM staging was analyzed. At the same time, the value of serum sPD-L1 and cancer embryo antigen (CEA) in clinical evaluation of advanced EGFR mutated lung adenocarcinoma was evaluated by analyzing the receiver operating characteristic (ROC) curve. A lower level of sPD-L1 level in EGFR mutation group [0.75(0.15-2.78) μg/L] was found compared with the control group [1.56(0.85-3.29) μg/L] (<0.001). The expression of sPD-L1 in PD group was significantly higher than that in DC group [1.175(0.62-2.78) μg/L vs 0.625(0.15-2.27) μg/L, <0.001]. High expression of sPD-L1 in the serum of patients with advanced EGFR mutated lung adenocarcinoma was closely correlated to lymph node metastasis and distant metastasis (χ=10.985, 4.662; both <0.05). The area under ROC curve of serum sPD-L1 and CEA was 0.893 (95% 0.830-0.956) and 0.745(95% 0.652-0.839) respectively. Youden index was the maximum when the cutoff value of sPD-L1 was set to 0.815 μg/L, and the sensitivity and specificity were 77.8% and 91.4%, respectively. After EGFR-TKI treatment, the level of sPD-L1 in the serum of patients with advanced EGFR mutated lung adenocarcinoma is lower, which suggests that sPD-L1 expression may depend on the regulation of EGFR signaling pathway. The level of sPD-L1 can reflect the clinical response of EGFR mutated lung adenocarcinoma to EGFR-TKI.
分析晚期表皮生长因子受体（EGFR）突变肺腺癌患者血清中可溶性程序性死亡配体1（sPD-L1）的表达，并探讨其临床意义。2015年5月至2016年7月，从苏州大学附属第二医院呼吸内科纳入72例EGFR突变的晚期肺腺癌患者（EGFR突变组）。另外纳入31例晚期EGFR野生型（WT）肺腺癌患者[EGFR WT组，通过支气管镜或经胸针吸活检（TNAB）的微量标本诊断，在性别、年龄和肿瘤分期方面与EGFR突变组匹配]作为对照。采用酶联免疫吸附测定（ELISA）试剂盒检测血清中sPD-L1蛋白表达。根据2个月EGFR酪氨酸激酶抑制剂（TKI）治疗的临床反应，将所有患者分为两组：疾病进展组（PD组）36例和疾病控制组（DC组）36例。分析两组外周血中sPD-L1水平。在EGFR突变组中，分析血清sPD-L1与TNM分期的关系。同时，通过分析受试者工作特征（ROC）曲线，评估血清sPD-L1和癌胚抗原（CEA）在晚期EGFR突变肺腺癌临床评估中的价值。结果发现，EGFR突变组sPD-L1水平[0.75（0.15 - 2.78）μg/L]低于对照组[1.56（0.85 - 3.29）μg/L]（<0.001）。PD组sPD-L1表达明显高于DC组[1.175（0.62 - 2.78）μg/L对0.625（0.15 - 2.27）μg/L，<0.001]。晚期EGFR突变肺腺癌患者血清中sPD-L1高表达与淋巴结转移和远处转移密切相关（χ=10.985，4.662；均<0.05）。血清sPD-L1和CEA的ROC曲线下面积分别为0.893（95% 0.830 - 0.956）和0.745（95% 0.652 - 0.839）。当sPD-L1的截断值设定为0.815 μg/L时，约登指数最大，敏感性和特异性分别为77.8%和91.4%。EGFR-TKI治疗后，晚期EGFR突变肺腺癌患者血清中sPD-L1水平降低，这表明sPD-L1表达可能依赖于EGFR信号通路的调节。sPD-L1水平可反映EGFR突变肺腺癌对EGFR-TKI的临床反应。
