A Lipid Metabolism-Related Gene Signature Stratifies Prognosis and Reflects Metabolic-Immune Heterogeneity in Head and Neck Squamous Cell Carcinoma.

Objective

Lipid metabolism-related genes (LMRGs) are crucial in head and neck squamous cell carcinoma (HNSCC) progression. This study aimed to construct and validate a prognostic model for HNSCC based on LMRGs.

Methods

Prognostic LMRGs were screened by analyzing RNA sequencing and clinical data from TCGA and GEO databases, and a prognostic model was constructed. Patients were divided into high- and low-risk groups according to the risk score. Further enrichment analysis, tumor microenvironment (TME) analysis, drug sensitivity analysis, and in vitro validation were performed.

Results

Eleven LMRGs (PER2, CTLA4, EPHX3, ABCB1, ANO1, TRIB3, PTX3, OLR1, DKK1, FABP4, and CDKN2A) were identified. Patients in the high-risk group had worse survival, and the risk score was an independent prognostic factor. A nomogram combining risk score and clinical characteristics accurately predicted survival. TME analysis revealed immune dysregulation in the high-risk group. Drug sensitivity analysis showed that the high-risk group was more sensitive to lovastatin. In vitro, lovastatin suppressed malignant behaviors and induced a transcriptomic shift toward a low-risk signature.

Conclusion

The results validate the biological significance of the model, highlight potential associations between lipid metabolism and the immune microenvironment in HNSCC, and provide a theoretical basis for further investigating metabolism-related therapeutic strategies.