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.

Cuproptosis: mechanisms and links with cancers

“…MKLN1-AS and AL031985.3 were both considered risk factors for patients with hepatocellular carcinoma [ 136 , 163 ], FOXD2-AS1 and LINC02154 were both considered risk factors for KIRC patients [ 175 – 177 ], AL513550.1 was suggested as a risk factor for CRC by different investigators [ 121 , 172 ], and AL132800.1 was thought to be a risk factor for HNSCC [ 178 , 179 ]. C6orf99 was regarded as a risk factor for patients with OSCC and HNSCC, two tumors with similar pathological types [ 152 , 173 ]. In contrast, upregulation of AC090587.1 and AC012313 was identified to be associated with a better prognosis in HNSCC patients [ 178 , 179 ], while AC073896.3 was used as a protective factor in the prognostic analysis of CRC patients [ 121 , 172 ].…”

“…However, most of these researchers predict the efficacy indirectly by the expression level of immune checkpoint genes or TIDE scores, only in some studies, investigators used the immunotherapy cohorts from the public databases to directly evaluate the prognosis of patients under immunotherapy. In most studies validated using immunotherapy cohorts, the low-risk group had a better prognosis for immunotherapy [ 152 , 156 , 158 , 173 , 194 ], except for those on glioma [ 140 , 141 ]. Moreover, in the study on UVM, it has been found that immunotherapy was ineffective in both populations [ 139 ].…”

The causal impact of complement C3d receptor 2 on head and neck cancer microenvironment and its implications for immunotherapy response prediction

“…The immune system plays a pivotal role in the oncogenesis and progression of HNC, highlighting the importance of exploring the intricate relationship between HNC and immune cell activities [ [4] , [5] , [6] ] [ [4] , [5] , [6] ] [ [4] , [5] , [6] ]. Identifying suitable biomarkers for predicting the immune microenvironment and the efficacy of immunotherapy in HNC patients stands as a critical objective [ 7 ]. These biomarkers hold the promise of revolutionizing treatment approaches by enabling personalized therapeutic strategies tailored to the unique immunological landscape of each patient's tumor [ 8 ].…”

An immune-related prognostic model predicts neoplasm-immunity interactions for metastatic nasopharyngeal carcinoma

“…Although no accepted immune-related risk model for predicting prognosis exists, the reported models have shown decent predictive validity in certain cancers (7)(8)(9)(10)(11)(12). The focus of immune-related prediction models is not only restricted to the genomic level but also extended to the transcriptome level, single-cell level, and so on (13)(14)(15)(16)(17)(18). However, there are not many studies on immune-related prognosis models integrating single-cell RNA and mRNA levels in metastatic NPC.…”