The Prognostic Role of Cuproptosis in Head and Neck Squamous Cell Carcinoma Patients: A Comprehensive Analysis

Abstract

Purpose. Head and neck squamous cell carcinoma (HNSCC) exhibits a high mortality and morbidity rate, and its treatment is facing clinical challenges. Cuproptosis, a copper-dependent cell death process, can help derive new forms of cancer therapies. However, the potential of cuproptosis-related genes (CRGs) as novel biomarkers for risk prediction, screening, and prognosis remains to be further explained in HNSCC. Methods. We built a prognostic multigene signature with CRGs, which is associated with the tumor immune microenvironment (TME) by gene set enrichment analysis (GSEA), in the TCGA cohort. Furthermore, we systematically correlated risk signature with immunological characteristics in TME including tumor-infiltrating immune cells (TIICs), immune checkpoints, T cell inflamed score, and cancer immunity cycles. We also thoroughly investigated the biological functions of cuproptosis-associated lncRNAs and its immunological characteristics. Results. CRGs-related prognostic model showed good prediction performance. A higher risk score was associated with a poorer overall survival (OS) than those with low-risk scores, according to the results of the survival analysis ( $p<0.0001$ ). The risk score was significantly related to the variable clinicopathological factors. Samples with high-risk scores had lower levels of CD8+ T cells infiltration. Immune therapy might be effective for the low-risk subtype of HNSCC patients ( $p<0.05$ ). Moreover, 11 differentially expressed lncRNAs as the independent prognostic factor could also predict TME in an accurate manner. Conclusion. Our study identified and validated novel cuproptosis-related biomarkers for HNSCC prognosis and screening, which offer better insights into developing accurate, reliable, and novel cancer therapies in the era of precision medicine.