A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma

BackgroundHead 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...

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Main Authors: Yingmiao Lin, Fangcai Wu, Xuchun Huang, Zhihan Zhang, Cantong Liu, Yiwei Lin, Yiwei Xu, Haipeng Guo, Chaoqun Hong
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538641/full
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author Yingmiao Lin
Fangcai Wu
Xuchun Huang
Zhihan Zhang
Cantong Liu
Yiwei Lin
Yiwei Xu
Haipeng Guo
Chaoqun Hong
author_facet Yingmiao Lin
Fangcai Wu
Xuchun Huang
Zhihan Zhang
Cantong Liu
Yiwei Lin
Yiwei Xu
Haipeng Guo
Chaoqun Hong
author_sort Yingmiao Lin
collection DOAJ
description BackgroundHead 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.MethodsWe 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.ResultThe 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.ConclusionWe 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.
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publisher Frontiers Media S.A.
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spelling doaj-art-b96e3d0794e34682aa1d24888d1ec24e2025-08-20T03:17:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15386411538641A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinomaYingmiao Lin0Fangcai Wu1Xuchun Huang2Zhihan Zhang3Cantong Liu4Yiwei Lin5Yiwei Xu6Haipeng Guo7Chaoqun Hong8Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Oncological Laboratory Research, Cancer Hospital of Shantou University Medical College, Shantou, ChinaBackgroundHead 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.MethodsWe 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.ResultThe 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.ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538641/fullmast cellhead and neck squamous cell carcinomasingle-cell sequencingimmune infiltrationimmunotherapy
spellingShingle Yingmiao Lin
Fangcai Wu
Xuchun Huang
Zhihan Zhang
Cantong Liu
Yiwei Lin
Yiwei Xu
Haipeng Guo
Chaoqun Hong
A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
Frontiers in Immunology
mast cell
head and neck squamous cell carcinoma
single-cell sequencing
immune infiltration
immunotherapy
title A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
title_full A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
title_fullStr A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
title_full_unstemmed A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
title_short A novel mast cell marker gene-related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
title_sort novel mast cell marker gene related prognostic signature to predict prognosis and reveal the immune landscape in head and neck squamous cell carcinoma
topic mast cell
head and neck squamous cell carcinoma
single-cell sequencing
immune infiltration
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1538641/full
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