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Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma (HNSCC). The integrative analysis of all the metabolism-related genes (MRGs) in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms. Therefore, this study was designed to establish a prognostic signature based on all the MRGs in HNSCC. Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study. Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts. The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases. The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups. GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation. The results of ESTIMATE, single-sample GSEA, CIBERSORT, and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics. The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity, indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately. In conclusion, this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.

In Silico analysis and linking of metabolism-related genes with the immune landscape in head and neck squamous cell carcinoma