A Signature of Immune-related Gene Pairs (IRGPs) for Risk Stratification and Prognosis of Oral Cancer Patients

Abstract

Background:With low response to present immunotherapy, it is imperative to identify new immune-related biomarkers for more effective immunotherapies for oral cancer.Methods:RNA profile for 390 oral cancer patients and 32 normal samples were downloaded from the Cancer Genome Atlas (TCGA) database and differentially expressed genes (DEGs) were analyzed. Immune genesets from Immportrepository were overlapped with DEGs. After implementing univariate Cox analysisand the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, key immune-related gene pairs (IRGPs) among the overlappedDEGs for predicting the survival riskwere obtained. Then, the cutoff of risk score was calculated by receiver operating characteristic (ROC) curve to stratify oral cancer patients into high and low-risk groups. Multivariate Cox analysis was used to analyze independent prognostic indicator fororal cancer.Besides, infiltration of immune cells, functional annotation and mutation analysis of IRGPs were conducted.Biological function correlated with IRGPs were enriched by Gene Set Enrichment Analysis (GSEA) method. Results: We identified698 differentially expressed genes (DEGs)in response to oral cancer. 17IRGPs among the DEGs were identified and integrated into a risk score model. Patients in high-risk group have significantly worse prognosis than those in low-risk group. Meanwhile, IRGPs model was identified as an independent prognostic factor for oral cancer. Different infiltration pattern of immune cells were found between high- and low-risk groups that more types of T and B cells were enriched in low-risk group. More immune-related signaling pathways were highly enriched in low-risk group. And Tenascin C (TNC) was the most frequently mutated genes. We have developed a novel 17-IRGPs signature for risk stratification and prognostic predication of oral cancer.Conclusion: Our study provides a foundation for improved immunotherapy and prognosis and is beneficial to the individualized management of oral cancer patients.