胆管癌手术患者程序性死亡配体1的表达与患者中性粒细胞淋巴细胞比例的关系及其临床意义研究
|
摘要
目的近年来胆管癌的发病率有逐渐增高的趋势,且缺乏有效的治疗手段。本研究旨在探讨胆管癌中PDL1的表达及作用。方法选取我院2015年1月至2017年5月间收治的46名接受手术切除肝外胆管癌患者,对其样本进行福尔马林固定石蜡包埋切片,用抗PD-L1抗体免疫组化染色评估PD-L1的表达。采用Fisher精确检验分析PD-L1和临床病理特征之间关联,采用Cox回归模型进行生存分析。结果在46个样本中,PD-L1在32个(70%)肿瘤细胞膜阳性表达。PD-L1表达的平均水平为1.75%(0-34.7)。PD-L1表达与IV期疾病(OR 3.98,P=0.046)和中性粒细胞/淋巴细胞比值(OR 5.36,P=0.018)显著相关。相对PD-L1阴性的肿瘤样本,PD-L1阳性与较差的总生存率有相关性,但未达到显著水平(7.2vs.7.9个月,P=0.32)。结论 PD-L1在胆管癌中广泛表达,但不能预测总生存期。PD-L1阳性与IV期疾病和高中性粒细胞/淋巴细胞比率呈显著相关。
Objective Effective treatments for cholangiocarcinoma(CCA)are still lacking.This study aimed to investigate the expression of PD-L1 and its relation to possible treatments for CCA.Methods 46 cases of patients with cholangiocarcinoma in our hospital from January 2015 to May 2017 were selected as study objects.Formalin-fixed paraffin-embedded tumor samples from the patients were retrieved.PD-L1 expression was evaluated by immunohistochemistry using anti-PD-L1 antibody.The association between PD-L1,clinico-pathological characteristics was analyzed using Fisher's exact test,and survival analysis was done with the Cox regression model.Results Out of 46 samples,32(70%)had positive PD-L1 expression in tumor cell membranes.The median level of PD-L1 expression was 1.75%(0-34.7).PD-L1 expression was significantly associated with stage IV disease(OR 3.98,P=0.046)and a high neutrophil/lymphocyte ratio(OR 5.36,P=0.018).PD-L1 positivity was associated with worse overall survival compared with those with a PD-L1 negative tumor but did not reach a level of significance(7.2 vs.7.9 months,P=0.32).Conclusion PD-L1 is widely expressed in CCA but was not predictive for overall survival.PD-L1 positivity was significantly associated with stage IV disease and a high neutrophil/lymphocyte ratio.
Objective Effective treatments for cholangiocarcinoma(CCA)are still lacking.This study aimed to investigate the expression of PD-L1 and its relation to possible treatments for CCA.Methods 46 cases of patients with cholangiocarcinoma in our hospital from January 2015 to May 2017 were selected as study objects.Formalin-fixed paraffin-embedded tumor samples from the patients were retrieved.PD-L1 expression was evaluated by immunohistochemistry using anti-PD-L1 antibody.The association between PD-L1,clinico-pathological characteristics was analyzed using Fisher's exact test,and survival analysis was done with the Cox regression model.Results Out of 46 samples,32(70%)had positive PD-L1 expression in tumor cell membranes.The median level of PD-L1 expression was 1.75%(0-34.7).PD-L1 expression was significantly associated with stage IV disease(OR 3.98,P=0.046)and a high neutrophil/lymphocyte ratio(OR 5.36,P=0.018).PD-L1 positivity was associated with worse overall survival compared with those with a PD-L1 negative tumor but did not reach a level of significance(7.2 vs.7.9 months,P=0.32).Conclusion PD-L1 is widely expressed in CCA but was not predictive for overall survival.PD-L1 positivity was significantly associated with stage IV disease and a high neutrophil/lymphocyte ratio.
引文
[1]谭勇,邱宝安,孟宇宏,等.去整合素-金属蛋白酶17过度表达对肝外胆管癌手术患者的预后价值[J].中华肝胆外科杂志,2015,21(10):674.
[2]McNamara MG,Templeton AJ,Maganti M,et al.Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer[J].Eur J Cancer,2014,50(9):1581.
[3]Lin G,Liu Y,Li S,et al.Elevated neutrophil-tolymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma[J].Oncotarget,2016,7(32):50963.
[4]Goeppert B,Frauenschuh L,Zucknick M,et al.Prognostic impact of tumour-infltrating immune cells on biliary tract cancer[J].Br JCancer,2013,109(10):2665.
[5]Motzer RJ,Escudier B,McDermott DF,et al.Nivolumab versus everolimus in advanced renal-cell carcinoma[J].N Engl J Med,2015,373(19):1803.
[6]Reck M,Rodriguez-Abreu D,Robinson AG,et al.Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J].N Engl J Med,2016,375(19):1823.
[7]Robert C,Long GV,Brady B,et al.Nivolumab in previously untreated melanoma without BRAF mutation[J].N Engl J Med,2015,372(4):320.
[8]Wu P,Wu D,Li L,et al.PD-L1and survival in solid tumors:Ameta-analysis[J].PLoS One,2015,10:e0131403.
[9]Zhou ZJ,Zhan P,Song Y.PD-L1over-expression and survival in patients with non-small cell lung cancer:a meta-analysis[J].Transl Lung Cancer Res,2015,4(2):203.
[10]Bae WK,Shim HJ,Choi YD,et al.Severe hypothyroidism in-duced by thyroid metastasis of cholangiocarcinoma[J].Cancer Res Treat,2009,41(1):56.
[11]Rozali EN,Hato SV,Robinson BW,et al.Programmed death ligand 2in cancer-induced immune suppression[J].Clin Dev Immunol,2012,2012:656340.
[12]Wang L,Ma Q,Chen X,et al.Clinical significance of B7-H1and B7-1expressions in pancreatic carcinoma[J].World J Surg,2010,34(5):1059.
[13]David R.PD-L1expression by circulating breast cancer cells[J].Lancet Oncol,2015,16(7):e321.
[14]Suleiman Y,Coppola D,Zibadi S,et al.Prognostic value of tumorinfltrating lymphocytes(TILs)and expression of PDL1in cholangiocarcinoma[J].J Clin Oncol,2015,33(3Suppl):294.
[15]Gani F,Nagarajan N,Kim Y,et al.Program death 1immune checkpoint and tumor microenvironment:Implications for patients with intrahepatic cholangiocarcinoma[J].Ann Surg Oncol,2016,23(8):2610.
[2]McNamara MG,Templeton AJ,Maganti M,et al.Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer[J].Eur J Cancer,2014,50(9):1581.
[3]Lin G,Liu Y,Li S,et al.Elevated neutrophil-tolymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma[J].Oncotarget,2016,7(32):50963.
[4]Goeppert B,Frauenschuh L,Zucknick M,et al.Prognostic impact of tumour-infltrating immune cells on biliary tract cancer[J].Br JCancer,2013,109(10):2665.
[5]Motzer RJ,Escudier B,McDermott DF,et al.Nivolumab versus everolimus in advanced renal-cell carcinoma[J].N Engl J Med,2015,373(19):1803.
[6]Reck M,Rodriguez-Abreu D,Robinson AG,et al.Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer[J].N Engl J Med,2016,375(19):1823.
[7]Robert C,Long GV,Brady B,et al.Nivolumab in previously untreated melanoma without BRAF mutation[J].N Engl J Med,2015,372(4):320.
[8]Wu P,Wu D,Li L,et al.PD-L1and survival in solid tumors:Ameta-analysis[J].PLoS One,2015,10:e0131403.
[9]Zhou ZJ,Zhan P,Song Y.PD-L1over-expression and survival in patients with non-small cell lung cancer:a meta-analysis[J].Transl Lung Cancer Res,2015,4(2):203.
[10]Bae WK,Shim HJ,Choi YD,et al.Severe hypothyroidism in-duced by thyroid metastasis of cholangiocarcinoma[J].Cancer Res Treat,2009,41(1):56.
[11]Rozali EN,Hato SV,Robinson BW,et al.Programmed death ligand 2in cancer-induced immune suppression[J].Clin Dev Immunol,2012,2012:656340.
[12]Wang L,Ma Q,Chen X,et al.Clinical significance of B7-H1and B7-1expressions in pancreatic carcinoma[J].World J Surg,2010,34(5):1059.
[13]David R.PD-L1expression by circulating breast cancer cells[J].Lancet Oncol,2015,16(7):e321.
[14]Suleiman Y,Coppola D,Zibadi S,et al.Prognostic value of tumorinfltrating lymphocytes(TILs)and expression of PDL1in cholangiocarcinoma[J].J Clin Oncol,2015,33(3Suppl):294.
[15]Gani F,Nagarajan N,Kim Y,et al.Program death 1immune checkpoint and tumor microenvironment:Implications for patients with intrahepatic cholangiocarcinoma[J].Ann Surg Oncol,2016,23(8):2610.