Increased programmed death ligand-1 expression predicts poor prognosis in hepatocellular carcinoma patients

Abstract

Purpose: Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue.

Methods: Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg's funnel plot.

Results: A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66-2.64, P<0.001) as well as poor DFS/RFS (HR =2.3, 95% CI: 1.46-3.62, P<0.001). In addition, increased PD-L1 expression was also associated with tumor differentiation (HR =1.51, 95% CI: 1-2.29, P=0.05), vascular invasion (HR =2.16, 95% CI: 1.43-3.27, P<0.001), and α-fetoprotein (AFP; HR =1.46, 95% CI: 1-2.14, P=0.05), but had no association with tumor stage, tumor size, hepatitis history, sex, age, or tumor multiplicity. No publication bias was found for all analyses.

Conclusion: This meta-analysis revealed that overexpression of PD-L1 was predictive for shortened OS and DFS/RFS in HCC. Furthermore, increased PD-L1 expression was associated with less differentiation, vascular invasion, and AFP elevation.

Keywords: hepatocellular carcinoma; meta-analysis; prognosis; programmed death ligand-1.

Figure 1

Flow diagram showing literature filtration process.

Figure 2

Forrest plot of HRs for the association of PD-L1 expression with (A) OS and (B) DFS/RFS in HCC patients. Note: Weights are from random effects analysis. Abbreviations: HRs, hazard ratios; OS, overall survival; PD-L1, programmed death ligand-1; DFS, disease-free survival; RFS, recurrence-free survival; HCC, hepatocellular carcinoma; CI, confidence interval; ES, effect size.

Figure 3

Begg’s funnel plot for publication bias tests in (A) OS and (B) DFS/RFS in HCC. Abbreviations: OS, overall survival; DFS, disease-free survival; RFS, recurrence-free survival; HCC, hepatocellular carcinoma; SE, standard error; lnhr, natural logarithm of hazard ratio.