Clinicopathological and Prognostic Role of Programmed Cell Death-1 in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background:Multiple studies have explored the prognostic role and clinical significance of the expression of the programmed cell death-1 (PD-1) gene in hepatocellular carcinoma (HCC). However, the results have been inconsistent. This study evaluatedPD-1expression and its clinical significance in patients with HCC, as well as the correlation between HCC pathological features and prognoses. Methods:All related research in PubMed, Embase, and Web of Science prior to October 31, 2019, was retrieved. The Newcastle-Ottawa Scale was used to evaluate the quality of the literature. Stata 14.0 statistical software was used to analyze the data, and the correlations betweenPD-1expression and the clinicopathological characteristics of patients were analyzed using the odds ratio (OR) and its 95% confidence interval (CI). The hazard ratio (HR) and its 95% CI were used to analyze the correlation betweenPD-1high expression and patient prognosis. Begg's test was used to evaluate publication bias. Results:A total of 581 patients were analyzed in the six studies included in the meta-analysis. Pooled analysis revealed that high levels ofPD-1expression did not correlate with overall survival (HR = 0.79; 95% CI: [0.41-1.54];p = 0.493). PD-1 positivity was associated with better disease-free survival (HR = 0.52; 95% CI: [0.38-0.72];p = 0.000). Furthermore, elevatedPD-1expression corrected with age (OR = 0.62, 95% CI: [0.41-0.96];p = 0.030) and alpha-fetoprotein levels (OR = 2.27, 95% CI: [1.46-3.55];p = 0.000), were not correlated with patientsex, tumor size, tumor multiplicity, hepatitis B virus history, tumor node metastasis stage and Barcelona Clinic Liver Cancer stage. Conclusions:This meta-analysis revealed thatPD-1expression may be a useful prognostic marker in HCC patients. Prospective clinical studies are needed to support these findings.