PD-L1在混合型肝癌中的表达及临床意义

Expression of PD-L1 and its clinical significance in combined hepatocellular-cholangiocarcinoma

目的检测混合型肝癌组织中程序性死亡蛋白配体1(PD-L1)的表达水平,探讨PD-L1表达水平与混合型肝癌患者临床特征和预后的关系。方法回顾性分析2011年1月至2019年12月天津医科大学肿瘤医院收治并行手术治疗的75例混合型肝癌患者的临床资料,其中男性61例,女性14例,年龄范围36~77岁,中位年龄55岁。应用免疫组化法检测75例癌组织中PD-L1表达水平,并分为PD-L1阴性组(n=66)和阳性组(n=9),并分析其与患者临床病理学特征及预后的关系。结果在低分化混合型肝癌的癌组织中PD-L1表达阳性比例为21.1%(8/38),高于中高分化癌组织的2.7%(1/37),差异有统计学意义(χ^(2)=4.366,P=0.037)。PD-L1阳性患者的中位无复发生存期(DFS)、总生存期(OS)分别为12.3个月和15.1个月,低于PD-L1阴性患者的中位DFS 14.4个月和OS 23.3个月,但仅DFS差异具有统计学意义(χ^(2)=4.052,P=0.044)。在多因素分析中,仅有大血管侵犯(DFS:HR=1.965,95%CI:1.119~3.450,P=0.019;OS:HR=1.781,95%CI:1.022~3.105,P=0.042)和淋巴结转移(DFS:HR=2.451,95%CI:1.1033~5.814,P=0.042;OS:HR=2.652,95%CI:1.120~6.279,P=0.027)是影响患者DFS、OS的独立预后因素。结论PD-L1在低分化混合型肝癌中的阳性比例较中高分化癌高;大血管侵犯和淋巴结转移是影响混合性肝癌患者预后的独立因素。

Objective To study the expression level of programmed death ligand 1(PD-L1)in combined hepatocellular-cholangiocarcinoma(cHCC-CCA)and its correlation with the clinical characteristics and prognosis.Methods The clinical data of 75 patients with cHCC-CCA undergoing surgery in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019,including 61 males and 14 females,with a median age of 55 years(36 to 77).Immunohistochemistry was conducted to determine the PD-L1 expression in tumor.The status of PD-L1 expression,clinicopathological data and prognosis of patients were analyzed.Results In low-differentiated cHCC-CCA tissues,the proportion of PD-L1 expression(21.1%,8/38)was higher than that in moderately to well-differentiated cHCC-CCA tissues(2.70%,1/37,χ^(2)=4.366,P=0.037).The median disease-free survival(DFS)and overall survival(OS)of PD-L1 positive patients were 12.3 and 15.1 months,respectively,lower than those of PD-L1 negative patients(14.4 and 23.3 months).The difference of DFS was statistically significant(χ^(2)=4.052,P=0.044).In multivariate analysis,major vascular invasion(DFS:HR=1.965,95%CI:1.119-3.450,P=0.019;OS:HR=1.781,95%CI:1.022-3.105,P=0.042)and lymph node metastasis(DFS:HR=2.451,95%CI:1.1033-5.814,P=0.042;OS:HR=2.652,95%CI:1.120-6.279,P=0.027)were identified as independent prognostic factors affecting DFS and OS.Conclusions The proportion of PD-L1 positive is higher inthe low-differentiated cHCC-CCA tissue compared to that in moderately to well-differentiated cHCC-CCA.The major vascular invasion and lymph node metastasis are independent factors affecting the prognosis of patients with cHCC-CCA.