ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1538641
This article is part of the Research TopicImmune Predictive and Prognostic Biomarkers in Immuno-Oncology: Refining the Immunological Landscape of CancerView all 30 articles
A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
Provisionally accepted
YingMiao Lin
FangCai WuXuChun HuangZhiHan Zhang
CanTong Liu
YiWei Lin
YiWei Xu*HaiPeng Guo*
ChaoQun Hong*- Cancer Hospital, College of Medicine, Shantou University, Shantou, China
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Background: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive and heterogeneous malignant tumor. Mast cells are one of the immune cells widely distributed in the tumor microenvironment (TME), and their immune response with various immune cells is essential in promoting or inhibiting tumor growth and metastasis. However, the role played by mast cells in HNSCC has yet to be fully clarified.Methods: We identified mast cell marker genes using single-cell RNA sequencing (scRNA-seq) from the GSE103322 of the GEO database. The HNSCC data from the TCGA databases was divided into training and validation groups. Cox regression and LASSO regression analyses were used to screen the prognostically relevant mast cell-related genes (MRGs) to construct a prognostic signature and differentiate risk groups. The receiver operating characteristic (ROC) and calibration curves were used to test the model’s accuracy. We revealed the immune landscape of HNSCC by immune infiltration, immune checkpoint levels, ESTIMATE, and TIDE analyses. Drug sensitivity analyses were used to understand the sensitivity of different risk groups to drug therapy.Result: The 14-MRGs prognostic signature classified patients into high- and low-risk groups, and the overall survival (OS) of the low-risk group was significantly higher than that of the high-risk group (p < 0.05). The areas under the ROC curves of the nomogram were 0.740, 0.737 and 0.707 at 1-, 3-, and 5-year, and they also showed better detection efficacy in the validation group than other independent predictors. The low-risk group had richer immune cell infiltration and higher immune scores. The lower TIDE score in the low-risk group demonstrates that patients in this group were less prone to have immune escape and more likely to benefit from immunotherapy. In addition, the low-risk group was more sensitive to a broader range of drugs than the high-risk group.Conclusion: We combined scRNA-seq data and bulk RNA-seq data to construct a 14-MRGs-based prognostic model capable of well predicting the prognosis of HNSCC patients. This model may also help identify patients who can benefit from immunotherapy.
Keywords: mast cell, Head and neck squamous cell carcinoma, single-cell sequencing, Immune infiltration, Immunotherapy
Received: 03 Dec 2024; Accepted: 23 Jun 2025.
Copyright: © 2025 Lin, Wu, Huang, Zhang, Liu, Lin, Xu, Guo and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
YiWei Xu, Cancer Hospital, College of Medicine, Shantou University, Shantou, China
HaiPeng Guo, Cancer Hospital, College of Medicine, Shantou University, Shantou, China
ChaoQun Hong, Cancer Hospital, College of Medicine, Shantou University, Shantou, China
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