IL20RB as a prognostic and immune-related biomarker in lung cancer: association with immune infiltration, tumor progression, and potential therapeutic targeting

Background: Lung cancer (LC) is the most prevalent and aggressive cancer worldwide. Immune checkpoint inhibitors (ICIs) can improve treatment outcomes, but a large number of patients still fail to respond to ICIs, suggesting the presence of additional synergistic inhibitory signaling pathways in the tumor microenvironment. Interleukin-20 receptor subunit beta (IL20RB), as a single transmembrane receptor protein, plays crucial roles in host defence, autoimmune responses, and tissue repair. This study aims to investigate the relationships of IL20RB with the prognosis and immune infiltration in LC patients. Methods: We obtained clinical data and RNA sequencing data of 1,149 samples from The Cancer Genome Atlas (TCGA). Differential expression analysis identified a total of 2,739 differentially expressed genes (DEGs), including 36 differentially expressed immune-related genes (DEIRGs). Further least absolute shrinkage and selection operator (LASSO) regression analysis identified 16 DEIRGs as significant prognostic factors, with IL20RB emerging as a key target due to its high expression in LC. Functional enrichment analysis, prognosis-related gene feature verification, immune cell infiltration analysis and protein-protein interaction (PPI) network construction were performed for IL20RB. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect IL20RB expression levels in cell lines, and potential drugs were screened. Results: Survival analysis revealed that a high IL20RB expression level was correlated with a poorer overall survival, suggesting its potential as a prognostic biomarker, with an area under the receiver operating characteristic curve (AUC) of 0.875. Functional enrichment analyses such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) indicated that IL20RB was involved in tumorigenesis and immunosuppressive pathways. Furthermore, IL20RB expression was positively correlated with multiple immune cells such as Th2 and natural killer (NK) CD56dim cells, and negatively correlated with eosinophils and Th17 cells. PPI networks constructed by STRING and GeneMANIA revealed the effects of IL20RB in immune receptor-mediated signaling activity and pathways. Pharmacological prediction analysis further identified that quercetin was a potential therapeutic agent targeting IL20RB. Conclusions: IL20RB is highly expressed in LC patients, correlates with tumor immune infiltration, and serves as an independent prognostic factor, suggesting its potential as a biomarker for immunotherapy and prognosis assessment in LC.