Comparative expression analysis of PD-1, PD-L1, and CD8A in lung adenocarcinoma

BACKGROUND: As a new strategy for advanced lung adenocarcinoma (LUAD), programmed cell death protein 1 (PD-1) pathway inhibitors have been used in clinic for several years. However, the roles of PD-1, programmed cell death-ligand 1 (PD-L1), and CD8A in LUAD are still unclear. In the study, we aimed to assess the correlation between the mRNA expression of these three factors and the clinical characteristics of LUAD, and to explore the influence of the PD-1/PD-L1/CD8A axis on the prognosis of LUAD. METHODS: The mRNA expression data and clinical characteristics of LUAD patients were retrieved from The Cancer Genome Atlas (TCGA). The optimal cutoff value for PD-1, PD-L1, and CD8A was determined by Cutoff Finder. The chi-square test was used to compare categorical variables. The prognostic effects of variables were analyzed using the Kaplan­­-Meier method and the Cox proportional hazards model. RESULTS: A total of 484 cases were enrolled in this study according to the selection process. The optimal cutoff values for identifying high/low mRNA expression were defined as 27.4 for PD-1, 29.41 for PD-L1, and 95.52 for CD8A. The high expression of PD-1 (P=0.015) and PD-L1 (P=0.027) was more frequent in women than in men. The high expression of PD-1 (P=0.003), PD-L1 (P=0.002), and CD8A (P=0.003) was associated with early T status, whereas CD8A showed a significantly higher expression in both the early stage (P=0.006) and early N stage groups (P=0.031). PD-1, PD-L1, and CD8A were significantly positively correlated among pairs (P<0.001). High expression of each of the three genes was associated with better prognosis (P=0.030 for PD-1, P=0.046 for PD-L1, P=0.019 for CD8A), although the relation did not reach statistical significance in the Cox regression hazards model. CONCLUSIONS: The study defined a group of cutoff values for PD-1, PD-L1, and CD8A to identify high and low mRNA expression in LUAD. The high expression of PD-1, PD-L1, and CD8A was associated with early T status, and CD8A showed significantly higher expression in both early stage and early N stage groups. Although the high expression of each of these three genes was associated with favorable overall survival (OS), they were not independent prognostic factors.