Integrating metabolism gene clusters and tumor immune microenvironment in head and neck squamous cell carcinoma

Abstract

Objective

To investigate the relationship between tumor metabolism and immune cell infiltration in Head and Neck Squamous Cell Carcinoma (HNSCC), aiming to identify novel biomarkers and potential therapeutic targets.

Methods

Seven major metabolic pathways were analyzed using Gene Set Variation Analysis (GSVA) in HNSCC cohorts to assess their correlation with overall survival (OS) and immune microenvironment characteristics. Unsupervised clustering was applied to identify metabolic subtypes, and differentially expressed metabolism-related genes (MRGs) were screened for prognostic relevance. A risk model was constructed based on 16 core MRGs. TNFAIP6 was further evaluated for its functional role through in vitro assays, including proliferation, migration, and invasion analyses.

Results

The activity of key metabolic pathways, such as glycolysis, oxidative phosphorylation, and fatty acid metabolism, significantly correlated with OS and immune infiltration patterns. Two distinct metabolic clusters (C1 and C2) were identified, with C1 associated with a more immune-enriched microenvironment. A total of 698 MRGs were linked to immune modulation and tumor progression. The risk model based on 16 MRGs effectively stratified patients by prognosis and immune infiltration status. TNFAIP6 was highly expressed in malignant cells and associated with immunosuppression, poor survival, and tumor progression. Functional experiments confirmed that TNFAIP6 knockdown inhibited tumor cell proliferation, migration, and invasion.

Conclusion

Metabolic reprogramming plays a critical role in shaping the immune landscape of HNSCC. TNFAIP6 represents a promising prognostic biomarker and potential therapeutic target for improving personalized treatment in HNSCC patients.