Abstract
Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N(6)-methyladenosine (m(6)A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of head and neck squamous cell carcinoma. Thus, combining indicated that immune-related gene prognostic index with m(6)A status should offer a better predictive power for immune responses. Methods: Head and neck squamous cell carcinoma samples from the cancer genome atlas (TCGA, n = 498) and gene expression omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the indicated that immune-related gene prognostic index through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m(6)A risk score was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to tumor immune microenvironment cell-infiltrating characteristics. Results: A composite score was determined based on indicated that immune-related gene prognostic index and m(6)A risk score. Head and neck squamous cell carcinoma patients in the cancer genome atlas were divided into four subgroups: A (IRGPI-High&m(6)A-risk-High, n = 127), B (IRGPI-High&m(6)A-risk-Low, n = 99), C (IRGPI-Low&m(6)A-risk-High, n = 99), and D (IRGPI-Low&m(6)A-risk-Low, n = 128), and overall survival (OS) was significantly different between subgroups (p < 0.001). The characteristics of tumor immune microenvironment cell infiltration in the four subgroups were significantly different in subgroups (p < 0.05). The receiver operating characteristic (ROC) curves show the predictive value of composite score for overall survival was superior to other scores. Conclusion: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for head and neck squamous cell carcinoma.