PD-1和PD-L1在Ⅳ a期鼻咽癌组织中的表达及临床意义

Expression of PD-1 and PD-L1 in patients with stage Ⅳa nasopharyngeal carcinoma and its clinical significance

检测鼻咽癌组织中PD-1和PD-L1的表达水平,探讨PD-1和PD-L1表达水平与鼻咽癌患者临床特征及预后关系。方法 应用免疫组织化学方法检测65例Ⅳa期鼻咽癌患者肿瘤组织中PD-1和PD-L1表达水平,分析两者表达水平与患者临床特征及长期生存间关系。对组间比较行χ^2检验或Fisher＇s精确概率法,相关分析采用Pearson检验;采用Kaplan-Meier进行生存分析,Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 阳性阈值为5%时肿瘤细胞表面PD-1和PD-L1阳性表达率分别为88%（57/65）、89%（58/65）,两者表达水平显著相关（P=0.003）;阳性阈值为10%时肿瘤细胞表面PD-1和PD-L1阳性表达率分别为38%（25/65）、58%（38/65）,两者表达水平趋于相关（P=0.080）。不同水平PD-1和PD-L1阳性表达与临床病理特征无关（P〉0.05）。单因素和多因素生存分析显示阳性阈值定为10%时PD-L1阳性表达者OS及PFS均较PD-L1阴性者短（OS：HR=3.95,95%CI为1.09-14.27,P=0.036;PFS：HR=2.73,95%CI为1.07-6.97,P=0.035）。结论 PD-1和PD-L1在鼻咽癌组织中呈高表达水平,且PD-L1表达水平与Ⅳa期鼻咽癌患者不良预后相关,在阳性阈值为10%时可更好地预测预后。

Objective To measure the expression levels of PD-1 and PD-L1 in the tumor tissues of patients with nasopharyngeal carcinoma （NPC） and to explore the association of their expression with the clinical characteristics and prognosis of NPC patients. Methods The expression levels of PD-1 and PD-L1 in 65 NPC patients were determined by immunohistochemistry, and an analysis was performed on the association of their expression with clinical characteristics and long-term survival in NPC patients. Comparisons between groups were made by the chi-square test or Fisher′s exact test, and the Pearson＇s test was used for correlation analysis. Survival rates were calculated using the Kaplan-Meier method, and the log-rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results Expression of PD-1 and PD-L1 was observed in 88%（57/65） and 89%（58/65） of tumor cell surfaces using a cut-off value of 5%, and 38%（25/65） and 58%（38/65） using a cut-off value of 10%. PD-1 expression was significantly correlated with PD-L1 expression using the cut-off value of 5%（P=0.003）, and a non-significant correlation was found between the expression levels of PD-1 and PD-L1 using the cut-off value of 10%（P=0.080）. There was no significant association between the positive expression rates of PD-1 and PD-L1 and clinicopathological characteristics （P〉0.05）. The univariate and multivariate survival analyses showed that using the cut-off value of 10%, the patients with positive PD-L1 expression had significantly reduced progression-free survival （hazard ratio[HR]=2.73, 95% confidence interval[CI]：1.07-6.97, P=0.035） and overall survival （HR=3.95, 95%CI：1.09-14.27, P=0.036） compared with those with negative PD-L1 expression. Conclusions PD-1 and PD-L1 are highly expressed in NPC tissues. The expression of PD-L1 is associated with the poor prognosis in patients with stage IVa NPC, and PD-L1 can better predict the poor prognosis using the cut-off value of 10%.