Evaluation of the roles and regulatory mechanisms of PD-1 target molecules in NSCLC progression

BACKGROUND: Targeted programmed cell death protein 1 (PD-1) therapy could effectively improve the long-term prognosis of patients with non-small cell lung cancer (NSCLC). The role of PD-1 targets in the progression of NSCLC has not been fully revealed. METHODS: The differentially expressed genes (DEGs) in patients’ blood after NSCLC treatment with PD-1 blocker nivolumab in the GSE141479 dataset were analyzed by GEO2R and identified in the TCGA database. The mechanism of action involved in the PD-1 target molecules via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network shows the relationship between PD-1 target molecules. The factors affecting the prognosis of NSCLC patients were identified via the COX regression analysis and survival analysis to build the risk model and nomogram. RESULTS: There were 64 DEGs in patients’ blood after nivolumab treatment and 48 DEGs in NSCLC tissues. The PD-1 target molecules involved cell proliferation, DNA replication, cell cycle, lung cancer, and other cellular processes. The prognostic factors CCNA2, CHEK1, DLGAP5, E2F8, FOXM1, HIST1H2BH, HJURP, MKI67, PLK1, TPX2, and TYMS, and the independent factors HIST1H2BH and PLK1, influenced the prognosis of NSCLC patients. HIST1H2BH and PLK1 were overexpressed in LUAD and LUSC tissues. The elevated expression levels of HIST1H2BH and PLK1 were related to the overall survival (OS) and the progression-free survival of NSCLC patients. High-risk NSCLC patients had a poor prognosis and were an independent factor influencing the poor prognosis of NSCLC patients. The high-risk model group was enriched with signaling mechanisms such as cell cycle, DNA replication, and homologous recombination. CONCLUSIONS: The risk model based on PD-1 target molecules was helpful to assess the prognosis of NSCLC patients. HIST1H2BH and PLK1 might become prognostic biomarkers of NSCLC patients.