PD-L1表达与胃癌发生发展的相关性Meta分析
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摘要
目的:采用Meta分析评价方法,探讨PD-L1表达与胃癌发生发展的相关性。方法:计算机检索Medline、Pub Med、EMBASE及中国知网等数据库,检索时间截止2017年8月1日公开发表关于PD-L1表达与胃癌的发生发展相关性的回顾性队列研究。采用STATA统计软件进行Meta分析,New castle-Ottawa Scale(NOS)量表进行文献质量评价,漏斗图评估文献的发表偏移。采用比值比(OR)及95%可信区间(CI)评价关联强度。结果:共纳入17篇文献(4 618例患者)进行Meta分析。PD-L1表达差异与EB病毒感染(OR=5.312,95%CI:2.106~13.401,P<0.05)、肿瘤浸润深度(OR=2.582,95%CI:1.316~5.065,P<0.05)、淋巴浸润(OR=1.317,95%CI:1.122~1.757,P<0.05)有关,而与TNM分期、肿瘤生长部位、淋巴结转移等无关。结论:PD-L1过表达在EB病毒感染、肿瘤浸润阳性、淋巴浸润阳性的胃癌患者中常发生。
Objective: To evaluate the relationship between the expression of PD-L1 and the development of gastric cancer by Meta-analysis. Methods: A retrospective cohort study of the relationship between PD-L1 expression and the development and progression of gastric cancer was published in the database of Medline,Pub Med,EMBASE and China Knowledge Network. The Meta-analysis was performed using STATA software,the New Castle-Ottawa Scale( NOS) scale was used to evaluate the literature quality,and the funnel map was used to evaluate the publication of the literature. The odds ratio( OR) and 95% confidence interval( CI) were used to evaluate the correlation intensity. Results: A total of 17 articles( 4 618 patients) were included in the Meta-analysis. PD-L1 expression was different from that of EBV infection( OR = 5. 312,95% CI: 2. 106-13. 401,P<0. 05),tumor infiltration depth( OR = 2. 582,95% CI: 1. 316-5. 065,P<0. 05),Lymphatic infiltration( OR = 1. 317,95% CI: 1. 122-1. 757,P <0. 05),but had nothing to do with sex,differentiation,TNM staging,tumor growth,etc. Conclusion: PD-L1 positive expression is more common in patients with EBV infection,positive tumor invasion,and lymphatic invasion positive gastric cancer.
Objective: To evaluate the relationship between the expression of PD-L1 and the development of gastric cancer by Meta-analysis. Methods: A retrospective cohort study of the relationship between PD-L1 expression and the development and progression of gastric cancer was published in the database of Medline,Pub Med,EMBASE and China Knowledge Network. The Meta-analysis was performed using STATA software,the New Castle-Ottawa Scale( NOS) scale was used to evaluate the literature quality,and the funnel map was used to evaluate the publication of the literature. The odds ratio( OR) and 95% confidence interval( CI) were used to evaluate the correlation intensity. Results: A total of 17 articles( 4 618 patients) were included in the Meta-analysis. PD-L1 expression was different from that of EBV infection( OR = 5. 312,95% CI: 2. 106-13. 401,P<0. 05),tumor infiltration depth( OR = 2. 582,95% CI: 1. 316-5. 065,P<0. 05),Lymphatic infiltration( OR = 1. 317,95% CI: 1. 122-1. 757,P <0. 05),but had nothing to do with sex,differentiation,TNM staging,tumor growth,etc. Conclusion: PD-L1 positive expression is more common in patients with EBV infection,positive tumor invasion,and lymphatic invasion positive gastric cancer.
引文
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[21]Qing Y,Li Q,Ren T,et al.Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer[J].Drug Des Devel Ther,2015,9:901-909.
[22]Wang LA,Wei X,Li Q,et al.The prediction of survival of patients with gastric cancer with PD-L1 expression using contrastenhanced ultrasonography[J].Tumour Biol,2016,37(6):7327-7332.
[23]Wu C,Zhu Y,Jiang J,et al.Immunohistochemical localization of programmed death-1 ligand-1(PD-L1)in gastric carcinoma and its clinical significance[J].Acta Histochem,2006,108(1):19-24.
[24]Zhang L,Qiu M,Jin Y,et al.Programmed cell death ligand 1(PD-L1)expression on gastric cancer and its relationship with clinicopathologic factors[J].Int J Clin Exp Pathol,2015,8(9):11084-11091.
[25]汪超,陈志红,魏法星,等.程序性死亡配体1在胃癌中的表达及其临床意义[J].江苏大学学报(医学版),2017,27(2):158-161.Wang C,Chen ZH,Wei FX,et al.Expression of programmed death ligand 1 in gastric cancer and its clinical value[J].J Jiangsu Univ(Medicine Edition),2017,27(2):158-161.
[26]卓静,时瑶.胃癌患者PD-L1、B7-H3的表达与肿瘤病理特征和预后的关系研究[J].西南国防医药,2016,26(6):602-605.Zhuo J,Shi Y.Study on relationship between expression of PD-L1and B7-H3 in patients with gastric cancer and the pathological features and prognosis of gastric cancer[J].Medical J National Defending Forces Southwest China,2016,26(6):602-605.
[27]朱卫伟.PD-1和PD-L1在胃癌组织中的表达及临床意义[J].河南医学研究,2017,26(18):3302-3304.Zhu WW.Expression and clinical significance of PD-L1 and PD-1in gastric carcinoma[J].Hennan Med Res,2017,26(18):3302-3304.
[28]Derks S,Liao X,Chiaravalli AM,et al.Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers[J].Oncotarget,2016,7(22):32925-32932.
[29]Thompson ED,Zahurak M,Murphy A,et al.Patterns of PD-L1expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma[J].Gut,2017,66(5):794-801.
[30]Fang W,Chen Y,Sheng J,et al.Association between PD-L1 expression on tumour-infiltrating lymphocytes and overall survival in patients with gastric cancer[J].J Cancer,2017,8(9):1579-1585.
[31]Tumeh PC,Harview CL,Yearley JH,et al.PD-1 blockade induces responses by inhibiting adaptive immune resistance[J].Nature,2014,515(7528):568-571.
[2]Chemnitz JM,Parry RV,Nichols KE,et al.SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation,but only receptor ligation prevents T cell activation[J].J Immunol,2004,173(2):945-954.
[3]Sun J,Xu K,Wu C,et al.PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies[J].Tissue Antigens,2007,69(1):19-27.
[4]马宝镇,高全立.抗PD-1及PD-L1在肿瘤治疗中的进展[J].中国免疫学杂志,2017,33(5):796-800.Ma BZ,Gao QL.Anti-PD-1 and PD-L1 in the treatment of cancer.[J].Chin J Immunol,2017,33(5):796-800.
[5]高建华,王加营,叶晓锋.PD-L1在恶性肿瘤中的表达及研究进展[J].中国免疫学杂志,2017,33(12):1917-1920.Gao JH,Wang JY,Ye XF.Expression and its research progress of PD-L1 in malignant tumor[J].Chin J Immunol,2017,33(12):1917-1920.
[6]Muro K,Chung H C,Shankaran V,et al.Pembrolizumab for patients with PD-L1-positive advanced gastric cancer(KEYNOTE-012):a multicentre,open-label,phase 1b trial[J].Lancet Oncol,2016,17(6):717-726.
[7]Wu P,Wu D,Li L,et al.PD-L1 and survival in solid tumors:Ameta-analysis[J].PLo S One,2015,10(6):1-15.
[8]Chakravarti N,Prieto VG.Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs:immunohistochemistry analysis[J].Transl Lung Cancer Res,2015,4(6):743-751.
[9]Stang A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J].Eur J Epidemiol,2010,25(9):603-605.
[10]Kawazoe A,Kuwata T,Kuboki Y,et al.Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte,mismatch repair,and Epstein-Barr virus status in a large cohort of gastric cancer patients[J].Gastric Cancer,2017,20(3):407-415.
[11]Hsu JT,Hsu CS,Le PH,et al.Immunochemotherapy benefits in gastric cancer patients stratified by programmed death-1 ligand-1[J].J Surg Res,2017,211:30-38.
[12]Saito R,Abe H,Kunita A,et al.Overexpression and gene amplification of PD-L1 in cancer cells and PD-L1+immune cells in Epstein-Barr virus-associated gastric cancer:the prognostic implications[J].Mod Pathol,2017,30(3):427-439.
[13]Cho J,Lee J,Bang H,et al.Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability[J].Oncotarget,2017,8(8):13320-13328.
[14]Li Z,Lai Y,Sun L,et al.PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer[J].Hum Pathol,2016,55:182-189.
[15]Kim JW,Nam KH,Ahn SH,et al.Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer[J].Gastric Cancer,2016,19(1):42-52.
[16]Dai C,Geng R,Wang C,et al.Concordance of immune checkpoints within tumor immune contexture and their prognostic significance in gastric cancer[J].Mol Oncol,2016,10(10):1551-1558.
[17]Eto S,Yoshikawa K,Nishi M,et al.Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection[J].Gastric Cancer,2016,19(2):466-471.
[18]Dong M,Wang HY,Zhao XX,et al.Expression and prognostic roles of PIK3CA,JAK2,PD-L1,and PD-L2 in Epstein-Barr virus-associated gastric carcinoma[J].Hum Pathol,2016,53:25-34.
[19]Chang H,Jung WY,Kang Y,et al.Programmed death-ligand 1expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+tumor infiltrating lymphocytes group[J].Oncotarget,2016,7(49):80426-80434.
[20]Geng Y,Wang H,Lu C,et al.Expression of costimulatory molecules B7-H1,B7-H4 and Fox P3+Tregs in gastric cancer and its clinical significance[J].Int J Clin Oncol,2015,20(2):273-281.
[21]Qing Y,Li Q,Ren T,et al.Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer[J].Drug Des Devel Ther,2015,9:901-909.
[22]Wang LA,Wei X,Li Q,et al.The prediction of survival of patients with gastric cancer with PD-L1 expression using contrastenhanced ultrasonography[J].Tumour Biol,2016,37(6):7327-7332.
[23]Wu C,Zhu Y,Jiang J,et al.Immunohistochemical localization of programmed death-1 ligand-1(PD-L1)in gastric carcinoma and its clinical significance[J].Acta Histochem,2006,108(1):19-24.
[24]Zhang L,Qiu M,Jin Y,et al.Programmed cell death ligand 1(PD-L1)expression on gastric cancer and its relationship with clinicopathologic factors[J].Int J Clin Exp Pathol,2015,8(9):11084-11091.
[25]汪超,陈志红,魏法星,等.程序性死亡配体1在胃癌中的表达及其临床意义[J].江苏大学学报(医学版),2017,27(2):158-161.Wang C,Chen ZH,Wei FX,et al.Expression of programmed death ligand 1 in gastric cancer and its clinical value[J].J Jiangsu Univ(Medicine Edition),2017,27(2):158-161.
[26]卓静,时瑶.胃癌患者PD-L1、B7-H3的表达与肿瘤病理特征和预后的关系研究[J].西南国防医药,2016,26(6):602-605.Zhuo J,Shi Y.Study on relationship between expression of PD-L1and B7-H3 in patients with gastric cancer and the pathological features and prognosis of gastric cancer[J].Medical J National Defending Forces Southwest China,2016,26(6):602-605.
[27]朱卫伟.PD-1和PD-L1在胃癌组织中的表达及临床意义[J].河南医学研究,2017,26(18):3302-3304.Zhu WW.Expression and clinical significance of PD-L1 and PD-1in gastric carcinoma[J].Hennan Med Res,2017,26(18):3302-3304.
[28]Derks S,Liao X,Chiaravalli AM,et al.Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers[J].Oncotarget,2016,7(22):32925-32932.
[29]Thompson ED,Zahurak M,Murphy A,et al.Patterns of PD-L1expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma[J].Gut,2017,66(5):794-801.
[30]Fang W,Chen Y,Sheng J,et al.Association between PD-L1 expression on tumour-infiltrating lymphocytes and overall survival in patients with gastric cancer[J].J Cancer,2017,8(9):1579-1585.
[31]Tumeh PC,Harview CL,Yearley JH,et al.PD-1 blockade induces responses by inhibiting adaptive immune resistance[J].Nature,2014,515(7528):568-571.