外周血sPD-L1在小细胞肺癌患者化疗期间变化及其临床意义
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摘要
目的:肿瘤微环境中,免疫相关机制使程序性死亡分子配体1(programmed death ligand 1,PD-L1)表达上调,从而异常激活PD-L1信号通路,介导肿瘤免疫逃逸。可溶性程序性死亡配体1(soluble programmed death ligand 1,sPD-L1)是PD-L1的一种存在形式。有研究证实sPD-L1在肺鳞癌及腺癌中的表达与疾病进展相关,而小细胞肺癌(small cell lung cancer,SCLC)恶性程度高侵袭性强,相关研究较少。本研究旨在观察sPD-L1在SCLC患者血浆中的表达变化及临床意义。方法:筛选2018年3月至2018年11月山西省肿瘤医院经病理学检查诊断为SCLC的初治患者94例作为试验组,选取同期健康体检者17例作为对照组,比较两组血浆sPD-L1的动态变化,并分析sPD-L1表达与TNM分期、远处转移以及胃泌素释放肽前体(pro-gastrin-releasing peptide,ProGRP)的相关性。结果:SCLC组血浆sPD-L1水平高于健康人组(P<0.05和P<0.01)。疾病缓解期的SCLC患者化疗后血浆sPD-L1水平比化疗前显著降低(P<0.01);疾病进展期患者化疗后血浆sPD-L1水平比化疗前显著升高(P<0.01)。SCLC患者sPD-L1异常高表达与疾病进展显著相关(P<0.05)。血浆sPD-L1表达与肿瘤标志物ProGRP呈正相关。结论:SCLC患者外周血浆sPD-L1的表达较健康人增高,且与疗效密切相关。
Objective: In tumor microenvironment, immune-related mechanisms up-regulate the expression of programmed death ligand 1(PD-L1), which abnormally activates PD-L1 signaling pathway and mediates tumor immune escape. Soluble programmed death ligand 1(sPD-L1) is a form of PD-L1. It has been confirmed that the expression of sPD-L1 in lung squamous cell carcinoma and adenocarcinoma is related to disease progression, while small cell lung cancer(SCLC) has a high degree of malignancy, strong invasiveness and few related studies. The purpose of this study was to observe the changes in expression of sPD-L1 in the plasma of SCLC patients and their clinical significance. Methods: A total of 94 patients with SCLC diagnosed by pathological examination in Shanxi Provincial Cancer Hospital from March 2018 to November 2018 were selected as test group, and 17 healthy persons in the same period were selected as control group. The dynamic changes of plasma sPD-L1 were compared between the two groups, and the correlations among the expression of sPD-L1 and TNM stage, distant metastasis, and pro-gastrin-releasing peptide(ProGRP) was analyzed. Results: The level of sPD-L1 in the test group was higher than that in the control group(P<0.05 and P<0.01, respectively). In patients with SCLC in the remission stage, the serum sPD-L1 level after chemotherapy was significantly lower than that before chemotherapy(P<0.01); in patients with advanced stage, the serum sPD-L1 level after chemotherapy was significantly higher than that before chemotherapy(P<0.01). The abnormal high expression of sPD-L1 in SCLC patients was significantly correlated with the progression of the disease(P<0.05). The expression of sPD-L1 in serum was positively correlated with the tumor marker ProGRP. Conclusions: The expression of s PDL1 in peripheral plasma of patients with SCLC is higher than that in healthy individuals and is closely related to the clinical effect.
Objective: In tumor microenvironment, immune-related mechanisms up-regulate the expression of programmed death ligand 1(PD-L1), which abnormally activates PD-L1 signaling pathway and mediates tumor immune escape. Soluble programmed death ligand 1(sPD-L1) is a form of PD-L1. It has been confirmed that the expression of sPD-L1 in lung squamous cell carcinoma and adenocarcinoma is related to disease progression, while small cell lung cancer(SCLC) has a high degree of malignancy, strong invasiveness and few related studies. The purpose of this study was to observe the changes in expression of sPD-L1 in the plasma of SCLC patients and their clinical significance. Methods: A total of 94 patients with SCLC diagnosed by pathological examination in Shanxi Provincial Cancer Hospital from March 2018 to November 2018 were selected as test group, and 17 healthy persons in the same period were selected as control group. The dynamic changes of plasma sPD-L1 were compared between the two groups, and the correlations among the expression of sPD-L1 and TNM stage, distant metastasis, and pro-gastrin-releasing peptide(ProGRP) was analyzed. Results: The level of sPD-L1 in the test group was higher than that in the control group(P<0.05 and P<0.01, respectively). In patients with SCLC in the remission stage, the serum sPD-L1 level after chemotherapy was significantly lower than that before chemotherapy(P<0.01); in patients with advanced stage, the serum sPD-L1 level after chemotherapy was significantly higher than that before chemotherapy(P<0.01). The abnormal high expression of sPD-L1 in SCLC patients was significantly correlated with the progression of the disease(P<0.05). The expression of sPD-L1 in serum was positively correlated with the tumor marker ProGRP. Conclusions: The expression of s PDL1 in peripheral plasma of patients with SCLC is higher than that in healthy individuals and is closely related to the clinical effect.
引文
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[19]Yu H,Batenchuk C,Badzio A,et al.PD-L1 Expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer[J].J Thorac Oncol,2017,12(1):110-120.
[20]Ott PAE,Hiret S,Kim D,et al.Pembrolizumab(MK-3475)in patients with extensive-stage small cell lung cancer:preliminary safety and efficacy results from KEYNOTE-028[J].J Clin Oncol,2015,(Suppl33):a7502.
[2]Temraz S,Charafeddine M,Mukherji D,et al.Trends in lung cancer incidence in Lebanon by gender and histological type over the period 2005-2008[J].J Epidemiol Glob Health,2017,7(3):161-167.
[3]Hann CL,Rudin CM.Management of small-cell lung cancer:incremental changes but hope for the future.Oncology(Williston Park)[J].Oncology(Williston Park),2008,22(13):1486-1492.
[4]Herbst RS,Soria JC,Kowanetz M,et al.Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J].Nature,2014,515(7528):563-567.
[5]Gatalica Z,Snyder C,Maney T,et al.Programmed cell death 1(PD-1)and its ligand(PD-L1)in common cancers and their correlation with molecular cancer type[J].Cancer Epidemiol Biomarkers Prev,2014,23(12):2965-2970.
[6]王晓景,施敏骅,陈永井.肺癌患者化疗前后外周血sPD-L1变化及其临床意义[J].江苏医药,2013,39(6):654-657.
[7]Langer CJ,Gadgeel SM,Borghaei H,et al.Carboplatin and pemetrexed with or without pembrolizumab for advanced,non-squamous non-small-cell lung cancer:a randomised,phase 2 cohort of the open-label KEYNOTE-021 study[J].Lancet Oncol,2016,17(11):1497-1508.
[8]Gandhi L,Rodríguez-Abreu D,Gadgeel S,et al.Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer[J].N Engl JMed,2018,378(22):2078-2092.
[9]Chen Y,Wang Q,Shi B,et al.Development of a sandwich ELISA for evaluating soluble PD-L1(CD274)in human sera of different ages as well as supernatants of PD-L1+cell lines[J].Cytokine,2011,56(2):231-238.
[10]施敏骅,邢玉斐,张增利,等.肺癌细胞中可溶性程序性死亡配体1的表达及其对T淋巴细胞功能的影响[J].中华肿瘤杂志,2013,35(2):85-88.
[11]Li Y,Xiao Y,Su M,et al.Role of soluble programmed death-1(sPD-1)and sPD-ligand 1 in patients with cystic echinococcosis[J].Exp Ther Med,2016,11(1):251-256.
[12]Zhang J,Gao J,Li Y,et al.Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics[J].Thorac Cancer,2015,6(4):534-538.
[13]Jin J,Si J,Liu Y,et al.Elevated serum soluble programmed cell death ligand 1 concentration as a potential marker for poor prognosis in small cell lung cancer patients with chemotherapy[J].Respir Res,2018,19(1):197.
[14]荆结线,杜丽莉,徐晓琴,等.ProGRP对小细胞肺癌的疗效与预后评价的价值[J].中华检验医学杂志,2013,36(8):708-712.
[15]Antonia SJ,Lopez-Martin JA,Bendell J,et al.Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer(CheckMate 032):a multicentre,open-label,phase 1/2 trial[J].Lancet Oncol,2016,17(7):883-895.
[16]Chung HC,Ros W,Delord JP,et al.Effcacy and safety of pembrolizumab in previously treated advanced cervical cancer.resuits from the phaseⅡKEYNOTE-158 study[J].J Clin Oncol,2019,(3):JCO1801265.
[17]Horn L,Mansfield AS,Szcz?sna A,et al.First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer[J].N Engl JMed,2018,379(23):2220-2229.
[18]Mok TSK,Wu YL,Kudaba I,et al.Pembrolizumab versus chemotherapy for previously untreated,PD-L1-expressing,locally advanced or metastatic non-small-cell lung cancer(KEYNOTE-042):a randomised,open-label,controlled,phase 3 trial[J].Lancet.2019,393(10183):1819-1830.
[19]Yu H,Batenchuk C,Badzio A,et al.PD-L1 Expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer[J].J Thorac Oncol,2017,12(1):110-120.
[20]Ott PAE,Hiret S,Kim D,et al.Pembrolizumab(MK-3475)in patients with extensive-stage small cell lung cancer:preliminary safety and efficacy results from KEYNOTE-028[J].J Clin Oncol,2015,(Suppl33):a7502.