晚期食管鳞癌患者血清sPD-L1与组织PD-L1的表达及与预后的关系
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摘要
目的:探讨血清可溶性程序性死亡配体1(sPD-L1)水平、组织PD-L1的表达对晚期食管鳞癌的预后判断价值。方法:收集晚期食管鳞癌患者127例,健康对照71名,ELISA法测定健康对照组及食管鳞癌组化疗前血清sPD-L1水平,同时检测炎性指标NLR、SII水平;免疫组化法测定食管鳞癌组织中PD-L1的表达,分析血清sPD-L1与组织PD-L1及NLR、SII的关系; Kaplan-Meier法和Cox回归分析晚期食管鳞癌患者预后影响因素。结果:食管鳞癌组血清sPD-L1、NLR、SII水平均高于健康对照组(P均<0. 05)。食管鳞癌患者血清sPD-L1水平与组织PD-L1表达无关(P=0. 619),但与炎性指标NLR、SII有关(P均<0. 05)。Kaplan-Meier法分析结果表明,sPD-L1水平、PD-L1表达和肿瘤部位与晚期食管鳞癌患者的预后有关(P均<0. 05)。Cox回归分析表明sPD-L1与PD-L1是晚期食管鳞癌预后的独立影响因素,高sPD-L1水平、PD-L1阳性的患者死亡风险增加(HR=1. 533,95%CI=1. 063-2. 211; HR=1. 703,95%CI=1. 058-2. 739)。结论:血清sPD-L1与组织PD-L1可用于晚期食管鳞癌患者的预后判定。
Aim: To explore the prognostic value of serum soluble programmed cell death ligand 1( sPD-L1) and tissue PD-L1 expression in advanced esophageal squamous cell carcinoma( ESCC). Methods: A total of 127 patients with advanced ESCC and 71 healthy volunteers( control group) were collected. Serum sPD-L1 in the control group and ESCC group was measured by ELISA. Meanwhile,NLR and SII,the inflammatory indexes in the two groups were calculated. The expression of PD-L1 in ESCC tissue was detected by immunohistochemistry. The relationship between serum sPD-L1 and tissue PD-L1,NLR,SII was analyzed. Kaplan-Meier analysis and Cox regression analysis were used to determine the risk factors on the prognosis. Results: Serum sPD-L1,NLR and SII in ESCC group were higher than those in control group( P < 0. 05).The level of sPD-L1 in ESCC was not associated with the expression of PD-L1( P = 0. 619),but it was associated with NLR and SII( P < 0. 05). Kaplan-Meier analysis indicated that sPD-L1,PD-L1 and tumor sites were related to the prognosis of advanced ESCC( P < 0. 05). Cox regression analysis showed that sPD-L1 and PD-L1 were independent prognostic factors for advanced ESCC,and high sPD-L1 level or PD-L1 positive patients had a significant increased risk of death( HR =1. 533,95% CI = 1. 063-2. 211; HR = 1. 703,95% CI = 1. 058-2. 739). Conclusion: Serum sPD-L1 level and tissue PDL1 expression can be prognostic indicators for patients with advanced ESCC.
Aim: To explore the prognostic value of serum soluble programmed cell death ligand 1( sPD-L1) and tissue PD-L1 expression in advanced esophageal squamous cell carcinoma( ESCC). Methods: A total of 127 patients with advanced ESCC and 71 healthy volunteers( control group) were collected. Serum sPD-L1 in the control group and ESCC group was measured by ELISA. Meanwhile,NLR and SII,the inflammatory indexes in the two groups were calculated. The expression of PD-L1 in ESCC tissue was detected by immunohistochemistry. The relationship between serum sPD-L1 and tissue PD-L1,NLR,SII was analyzed. Kaplan-Meier analysis and Cox regression analysis were used to determine the risk factors on the prognosis. Results: Serum sPD-L1,NLR and SII in ESCC group were higher than those in control group( P < 0. 05).The level of sPD-L1 in ESCC was not associated with the expression of PD-L1( P = 0. 619),but it was associated with NLR and SII( P < 0. 05). Kaplan-Meier analysis indicated that sPD-L1,PD-L1 and tumor sites were related to the prognosis of advanced ESCC( P < 0. 05). Cox regression analysis showed that sPD-L1 and PD-L1 were independent prognostic factors for advanced ESCC,and high sPD-L1 level or PD-L1 positive patients had a significant increased risk of death( HR =1. 533,95% CI = 1. 063-2. 211; HR = 1. 703,95% CI = 1. 058-2. 739). Conclusion: Serum sPD-L1 level and tissue PDL1 expression can be prognostic indicators for patients with advanced ESCC.
引文
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[22]JIANG YB,LO AW,WONG A,et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma[J]. Oncotarget,2017,8(18):30175
[2] GOTWALS P,CAMERON S,CIPOLLETTA D,et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy[J]. Nat Rev Cancer,2017,17(5):286
[3] BOUSSIOTIS VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway[J]. N Engl J Med,2016,375(18):1767
[4] ZHANG G,HOU J,SHI J,et al. Soluble CD276(B7-H3)is released from monocytes,dendritic cells and activated T cells and is detectable in normal human serum[J]. Immunology,2008,123(4):538
[5] DE LA FUENTE H,CIBRIAN D,SANCHEZ-MADRID F. Immunoregulatory molecules are master regulators of inflammation during the immune response[J]. FEBS Lett,2012,586(18):2897
[6] OKUMA Y,HOSOMI Y,NAKAHARA Y,et al. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer[J]. Lung Cancer,2017,104:1
[7] FINKELMEIER F,CANLIO,TAL A,et al. High levels of the soluble programmed death-ligand(s PD-L1)identify hepatocellular carcinoma patients with a poor prognosis[J]. Eur J Cancer,2016,59:152
[8] ZHU YM,LI MH,MU DB,et al. CD8+/FOXP3+ratio and PD-L1 expression associated with survival in p T3N0M0 stage esophageal squamous cell cancer[J]. Oncotarget,2016,7(44):71455
[9] ZHANG J,GAO J,LI YY,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
[10]AZIZ MH,SIDERAS K,AZIZ NA,et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on Bilirubin levels:a retrospective multicenter cohort study[J]. Ann Surg,2019,270(1):139
[11]HA H,NAM AR,BANG JH,et al. Soluble programmed death-ligand 1(s PDL1)and neutrophil-to-lymphocyte ratio(NLR)predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy[J]. Oncotarget,2016,7(47):76604
[12]KRUGER S,LEGENSTEIN ML,ROESGEN VA,et al. Serum levels of soluble programmed death protein 1(s PD-1)and soluble programmed death ligand 1(s PD-L1)in advanced pancreatic cancer[J]. Oncoimmunology,2017,6(5):e1310358
[13]JIN JJ,SI JM,LIU YH,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]HARABUCHI Y,TAKAHARA M,KISHIBE K,et al. Nasal natural killer(NK)/T-cell lymphoma:clinical,histological,virological,and genetic features[J]. Int J Clin Oncol,2009,14(3):181
[15]HAN XE,GU YK,LI SL,et al. Pre-treatment serum levels of soluble programmed cell death-ligand 1 predict prognosis in patients with hepatitis B-related hepatocellular carcinoma[J]. J Cancer Res Clin Oncol,2019,145(2):303
[16]DONG YA,SUN Q,ZHANG XW. PD-1 and its ligands are important immune checkpoints in cancer[J]. Oncotarget,2017,8(2):2171
[17]ZHOU J,MAHONEY KM,GIOBBIE-HURDER A,et al.Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade[J]. Cancer Immunol Res,2017,5(6):480
[18]SUNSHINE J,TAUBE JM. PD-1/PD-L1 inhibitors[J].Curr Opin Pharmacol,2015,23:32
[19]QU HX,ZHAO LP,ZHAN SH,et al. Clinicopathological and prognostic significance of programmed cell death ligand 1(PD-L1)expression in patients with esophageal squamous cell carcinoma:a meta-analysis[J]. J Thorac Dis,2016,8(11):3197
[20]KIM R,KEAM B,KWON D,et al. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma[J]. World J Gastroenterol,2016,22(37):8389
[21]关嵩,王军,刘月平,等.食管鳞癌组织PD-L1表达临床意义[J].中华肿瘤防治杂志,2018,25(11):778
[22]JIANG YB,LO AW,WONG A,et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma[J]. Oncotarget,2017,8(18):30175