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A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer

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Abstract

Background

Cuproptosis is a novel form of cell death that is highly related to mitochondrial metabolism and mediated by protein lipoacetylation. This study systematically assessed the differential expression and genetic alterations of cuproptosis-related genes (CRGs) in head and neck squamous-cell carcinoma (HNSCC) and constructed CRG risk models to predict survival in patients with HNSCC.

Methods

We investigated the expression of 19 CRGs in HNSCC and noncancerous tissues, and the relationship between mutation load, immune infiltration, and clinical features was examined based on data from public databases. CRG risk models were constructed by univariate Cox analysis and lasso regression and validated by independent datasets for their accuracy in predicting survival outcomes in patients with HNSCC. The expression distribution of CRGs in HNSCC cells was further explored in the HNSCC single-cell sequencing dataset.

Results

NFE2L2, ATP7A, FDX1, LIAS, DLD, DLAT, PDHB, MTF1 and DBT were highly expressed in noncancerous samples, while GLS, CDKN2A and DLST were highly expressed in HNSCC samples (p < 0.05). Gene copy number variation frequency (CNV) revealed CDKN2A, FDX1 and DLAT copy number deletions and LIPT2 and NFE2L2 copy number increases. Ten CRGs were used to construct a risk model to predict overall survival (OS) in HNSCC, yielding reduced OS in the high-risk group compared to the low-risk group, training group (p = 9.733e − 05), and testing group (p = 0.040). The CRG risk model was significantly correlated with various immune cells, regulatory T cells (Tregs) and memory B cells were significantly negatively correlated (p = 0.027, p = 0.00084), and resting CD4 memory T cells was significantly positively correlated (p = 9e − 04). Most CRGs significantly affected the clinical characteristics of HNSCC. NFE2L2, SLC31A1, PDHA1, CDKN2A and DBT were highly expressed in epithelial cells of HNSCC, while SLC31A1, DBT and NFE2L2 were highly expressed in T cells, and SLC31A1 in B cells. In monocytes, NFE2L2, SLC31A1 and PDHA1 were highly expressed.

Conclusion

The CRG risk model can be used as a potential prognostic factor for HNSCC patients and may provide new insights into cancer treatment from the perspective of copper metabolism.

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Data availability

Publicly available datasets were analyzed in this study. This data can be found here: [https://portal.gdc.cancer.gov/], [https://www.ncbi.nlm.nih.gov/geo/]. The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

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Acknowledgements

We thank the study participants and research staff for their contributions and commitment to this study. The first author would like to thank Dr. Wei Xia, Department of the First Affiliated Hospital of Guangxi Medical University, for his support and careful supervision of this study, which provided inspiration and added details for this study and Dr. Feng Qingyuan, Department of Otorhinolaryngology, Renmin Hospital of Wuhan University for her encouragement, patient companionship and health care during the study period.

Funding

This work was supported by the Chongqing Municipal Health and Wellness Commission, Clinical and experimental study of terahertz time-domain system in judging pathological margin of hypopharyngeal carcinoma, [2021MSXM018]. A grant from the Chongqing Medical University Postgraduate Research Innovation Project, Clinical and experimental study of terahertz time-domain system in the determination of pathological margin of laryngeal carcinoma, [CYS21253].

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Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Chongqing General Hospital, No. 118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China

    Xu Jiang, Jing Ke, Lifeng Jia, Xiang An, Haiyu Ma, Zhongwan Li & Wei Yuan

  2. Department of Otorhinolaryngology-Head and Neck Surgery, Chongqing Hospital, University of the Chinese Academy of Sciences (SCAS Chongqing), Chongqing, China

    Xu Jiang, Jing Ke, Lifeng Jia, Xiang An, Haiyu Ma, Zhongwan Li & Wei Yuan

  3. Chongqing Medical University, Chongqing, China

    Jing Ke & Wei Yuan

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  1. Xu Jiang
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  2. Jing Ke
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Contributions

XJ, JK, LJ, XA, HM and ZL conducted data analysis and verification. XJ and WY conceived the study. XJ and JK drafted the manuscript. XJ, JK, LJ, XA, HM and ZL collected the data. WY and ZL commented on previous versions of the manuscript.

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Correspondence to Wei Yuan.

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Jiang, X., Ke, J., Jia, L. et al. A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer. J Cancer Res Clin Oncol 149, 203–218 (2023). https://doi.org/10.1007/s00432-022-04471-7

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