Prognostic value of programmed cell death ligand 1 (PD-L1) for hepatocellular carcinoma: a meta-analysis.

Xiao-Song Li,Tao Jiang,Jun-Wei Li,Hui Li

doi:10.1042/bsr20200459

Xiao-Song Li, Tao Jiang + Show 2 more

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https://doi.org/10.1042/bsr20200459

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Journal: Bioscience reports	Publication Date: Apr 17, 2020
Citations: 37	License type: CC BY 4.0

Affiliation: Jilin University, Union Hospital

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and ranks as the second most prevalent cause of cancer-related mortality [1]
The results indicated that high soluble programmed cell death ligand 1 (PD-L1) levels were associated with worse overall survival (OS) (HR: 2.93; 95% 95% confidence interval (CI): 2.20–3.91; P < 0.00001)
16 studies analyzed the relationship between membrane-bound PD-L1 (mPD-L1) expression and OS [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], seven studies analyzed the relationship between mPD-L1 expression and disease-free survival (DFS) [14,21,23,25,26,30,31], and six studies analyzed the relationship between mPD-L1 expression and relapse-free survival (RFS) [15,19,20,22,27,28]

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and ranks as the second most prevalent cause of cancer-related mortality [1]. Viral infection is one of the main causes of liver cirrhosis and HCC [1]. After a chronic viral infection, persistent innate and adaptive immune responses lead to immune tolerance and tumor formation. The programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a critical role in the development of chronic infection, in escaping from tumor immune response, and tumor microenvironment formation [2]. In cell-mediated immunity, T-cell receptors are activated to recognize the tumor antigen expressed by tumor cell MHC molecules, License 4.0 (CC BY)

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