PD - L1 and PD - L2 expression correlated genes in non-small-cell lung cancer

Background Programmed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD - L1 and PD - L2 expression correlated genes in NSCLC. Methods We performed comparative retrospective analyses to identify PD - L1 and PD - L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results Analysis of the CCLE dataset Lung_NSC identified expression correlation between PD - L1 and PD - L2 . Moreover, we identified expression correlation between 489 genes and PD - L1 , 191 genes and PD - L2 , and 111 genes for both. PD - L1 and PD - L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD - L1 , 914 genes and PD - L2 , and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD - L1 , 326 genes and PD - L2 , and 13 genes for both. Only a few genes expression correlated with PD - L1 and PD - L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD - L1 in Lung_NSC, for PD - L2 in LUSC, and for both PD - L1 and PD - L2 in LUAD. In LUSC, PD - L1 , and to a lesser extent PD - L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD - L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD - 1 and CD80 expression correlated with both PD - L1 and PD - L2 in LUAD. CD80 expression correlated with PD - L2 in LUSC. Conclusions We present gene signatures associated with PD - L1 and PD - L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.