An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma

Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified. Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC. Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01–1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4–8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6–11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4(+) T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042–1.081], p-value = 1.6e-10) of HNSC patients. Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC.