Association of cuproptosis-related signature with the prognosis of patients with head and neck squamous cell carcinoma

Abstract

Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis because of their high recurrence and metastasis rates. Cuproptosis is a novel type of copper-dependent cell death that differs from apoptosis, necroptosis, and cytosolic scorch death. We designed and validated an individualized cuproptosis-related gene (CRG) signature for risk evaluation and prognostic prediction in HNSCC patients. Ninety differentially expressed CRGs were found in HNSCC. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the functional involvement of CRGs in the Cancer Genome Atlas (TCGA) HNSCC cohort. A CRG signature was created using 10 genes after univariate and multivariate analysis. Kaplan Meier (KM) analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Multivariate regression analysis identified risk scores based on prognostic characteristics as independent prognostic indicators of HNSCC. Moreover, risk models are related to tumor mutational burden (TMB), tumor-infiltrating immune cells (TICs), immune checkpoints, clinical characteristics, and antitumor drug susceptibility. Furthermore, we found that CuCl₂ treatment promoted cuproptosis in HNSCC cells, and that the expression levels of cuproptosis-related genes were altered by different doses of CuCl₂. In summary, understanding the detailed molecular mechanisms of cuproptosis and its impact on overall survival (OS), and identifying potential therapeutic targets for HNSCC will provide potential insights for treatment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cuproptosis
• HNSCC
• prognostic
• immune infiltration
• TCGA

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

Ethical approval is not needed because this study does not contain animals and other human subjects.

Authors contributions

Y.L. and C.S. designed the project and wrote the manuscript. F.G., J.Y., H.X. and B.Y. performed collection and/or assembly of data, data analysis, and interpretation. Y.W. and R.C. gave final approval of the manuscript and financial support. All authors read and approved the final manuscript.

Data availability statement

The datasets presented in this study can be found in online repositories. The name of the repository can be found below: The Cancer Genome Atlas (TCGA) https://tcga-data.nci.nih.gov/tcga/.

Additional information

Funding

This study was supported by Research Fund of Anhui Institute of translational medicine (2022zhyx-C86) and 2022 Disciplinary Construction Project in School of Dentistry, Anhui Medical University (2022xkfyhz01)