Prognostic Value of PD-L1 mRNA Sequencing Expression Profile in Non-Small Cell Lung Cancer

Background: Immune checkpoint inhibitors that target the programmed cell death protein ligand 1 (PD-L1) pathway have shown benefit for the treatment of metastatic non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 independent of immunotherapy is still unclear, with conflicting results reported between PD-L1 expression and patient survival. Our aim was to correlate PD-L1 mRNA level with clinical and pathologic factors and to investigative the prognostic value of PD-L1 mRNA in all stages of NSCLC. Methods: Gene expression and clinical data were obtained from public repositories in The Cancer Genome Atlas from the National Cancer Institute. Genotype-Tissue Expression was used to compare with normal tissue expression analysis. Results: A total of 985 patients met inclusion criteria, among whom 79.6% were stage I to II, 16.5% were stage III, and 3.5% were stage IV, representing 495 adenocarcinoma and 490 squamous cell carcinoma (SCC). PD-L1 mRNA gene expression in lung cancers was higher than in most other tumor and normal tissue types and was significantly higher in lung SCC than adenocarcinoma (p < 0.001). PD-L1 mRNA expression was associated with pathologic stage in SCC and with smoking status in adenocarcinoma of the lung. However, none of the cutoff values of PD-L1 mRNA expression were prognostic of overall survival. Conclusions: Our results suggest that the value of PD-L1 mRNA in prognosticating outcome in lung cancer is limited. Further studies are needed to identify novel prognostic biomarkers other than PD-L1 that are associated with improved patient survival. Identification of further prognostically important biomarkers may prove useful in identifying patients suitable for immunotherapy.