Identification and validation of Osteopontin and receptor for hyaluronic acid-mediated motility (RHAMM, CD168) for potential immunotherapeutic significance of in lung squamous cell carcinoma

Abstract

BackgroundLung cancer is the leading cause of cancer-related deaths. Immunotherapy is a promising therapeutic approach, but the population best suited to immunotherapy is yet to be determined. Materials and methodsLung squamous cell carcinoma (LUSC) was chosen as the object for the present study. Four gene expression profiles were retrieved from the GEO database. 141 differentially expressed genes (DEGs) were detected in LUSC tissues and normal tissues by the GEO2R tool and Venn diagram software. Results34 candidate genes were selected for further analysis. A Kaplan–Meier survival plot further isolated 29 of 34 genes and after re-validation using gene expression profiling interactive analysis and pathway enrichment, Bonferroni correction was used to adjust P values, results showed that two genes (CD168 and OPN) were markedly enriched in the extracellular matrix (ECM)-receptor interaction pathway. We believe this pathway and genes may be tightly involved in the LUSC tumor immune microenvironment. We conducted a further cellular study to knock-down OPN in H520 cells using siRNA. The expression of CD168 was reduced in siRNA-OPN H520 cells (P < 0.05). Our results indicate that the arrest of CD168 occurs after the downregulation of the OPN protein, suggesting that OPN participates in ECM-receptor interactions. ConclusionsBy using integrated bioinformatics, we have identified CD168 and OPN as DEGs with poor prognosis in LUSC and have validated their interaction in the ECM receptor pathway. These genes could be potential diagnostic and therapeutic targets for LUSC patients undergoing immunotherapy.