Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin, China.
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200459.
The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12-1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85-1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81-2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20-3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16-1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54-0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55-0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06-10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.
程序性死亡配体 1（PD-L1）在肝细胞癌（HCC）中的表达的预后作用已得到广泛研究，但结果存在争议。在这项综合荟萃分析中，我们阐明了 PD-L1 在 HCC 中的临床价值。系统地检索了 Cochrane 图书馆、EMBASE 和 PubMed 中的相关研究，检索时间截至 2019 年 6 月 27 日。使用风险比（HR）及其 95％置信区间（95％CI），对 PD-L1 对 HCC 患者的总生存期（OS）、无病生存期（DFS）和无复发生存期（RFS）的预后影响进行验证。共有 23 项研究，涉及 3529 例患者，纳入本荟萃分析。汇总结果显示，高膜结合 PD-L1（mPD-L1）表达与较差的 OS 相关（HR：1.42；95％CI：1.12-1.80；P = 0.004），但与 RFS（HR：1.14；95％CI：0.85-1.54；P = 0.39）和 DFS（HR：1.36；95％CI：0.81-2.28；P = 0.25）无显著相关性。结果还表明，高可溶性 PD-L1（sPD-L1）水平与较差的 OS 相关（HR：2.93；95％CI：2.20-3.91；P < 0.00001）。此外，高 mPD-L1 表达与高甲胎蛋白（AFP）水平相关（OR = 1.46；95％CI：1.16-1.84；P = 0.001），乙型肝炎（OR = 0.72；95％CI：0.54-0.98；P = 0.03），肿瘤分化不良（OR = 0.68；95％CI：0.55-0.84；P = 0.03）和肿瘤浸润淋巴细胞（OR = 3.39；95％CI：1.06-10.91；P = 0.04）相关。mPD-L1 表达与年龄、肿瘤数量、性别、肿瘤大小、肝硬化、血管侵犯、肿瘤包膜、TNM 分期无显著相关性。该研究表明，肿瘤组织中高 mPD-L1 表达和高 sPD-L1 水平与 HCC 患者的 OS 较短有关。此外，mPD-L1 的过表达与肿瘤分化不良、乙型肝炎、AFP 升高和肿瘤浸润淋巴细胞显著相关。
