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Full Length Article | Open Access

Identification of ferroptosis-associated tumor antigens as the potential targets to prevent head and neck squamous cell carcinoma

Qiming ZhaiaZhiwei WangbHan TangaShanshan HuaMeihua Chenc( )Ping Jia( )
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, Sichuan 610041, China

Peer review under responsibility of Chongqing Medical University.

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Abstract

Head and neck squamous cell carcinoma (HNSC) represents nearly 90% of all head and neck tumors. The current treatment modality for HNSC patients primarily involves surgical intervention and radiotherapy, but its therapeutic efficacy remains limited. The mRNA vaccine based on tumor antigens seems promising for cancer treatment. Ferroptosis, a novel form of cell death, is linked to tumor progression and cancer immunotherapy. Nevertheless, the effectiveness of ferroptosis-associated tumor antigens in treating HNSC remains uncertain. In this study, we identified three ferroptosis-associated tumor antigens, namely caveolin1 (CAV1), ferritin heavy chain (FTH1), and solute carrier 3A2 (SLC3A2), as being overexpressed and mutated based on data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. These antigens were strongly associated with poor prognosis and infiltration of antigen-presenting cells in HNSC. We further identified two ferroptosis subtypes (FS1 and FS2) with distinct molecular, cellular, and clinical properties to identify antigen-sensitive individuals. Our findings indicate that FS1 exhibits an immune “hot” phenotype, whereas FS2 displays an immune “cold” phenotype. Additionally, differential expression of immunogenic cell death modulators and immune checkpoints was observed between these two immune subtypes. Further exploration of the HNSC’s immune landscape revealed significant heterogeneity among individual patients. Our findings suggest that CAV1, FTH1, and SLC3A2 are potential targets to prevent HNSC in FS2 patients. Overall, our research reveals the potential of ferroptosis-associated mRNA vaccines for HNSC and identifies an effective patient population for vaccine treatment.

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Genes & Diseases
Article number: 101212
Cite this article:
Zhai Q, Wang Z, Tang H, et al. Identification of ferroptosis-associated tumor antigens as the potential targets to prevent head and neck squamous cell carcinoma. Genes & Diseases, 2024, 11(6): 101212. https://doi.org/10.1016/j.gendis.2024.101212

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Received: 04 June 2023
Revised: 22 November 2023
Accepted: 05 December 2023
Published: 19 January 2024
© 2024 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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