Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: A systematic review and meta-analysis

Abstract

OBJECTIVES: Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS: We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS: A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P < 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23-34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS: This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PDL1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.