Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort

Abstract Background Head and neck squamous cell carcinomas (HNSCs) are among the most common tumors worldwide. Despite the availability of various diagnostic and therapeutic strategies, the incidence and mortality rates of HNSC remain high. Cancer-associated fibroblasts (CAFs), as a major component...

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Main Authors: Ling Zhong, Yixin Qiao, Shasha He, Yangju Fu, Jian Zou
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02507-1
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author Ling Zhong
Yixin Qiao
Shasha He
Yangju Fu
Jian Zou
author_facet Ling Zhong
Yixin Qiao
Shasha He
Yangju Fu
Jian Zou
author_sort Ling Zhong
collection DOAJ
description Abstract Background Head and neck squamous cell carcinomas (HNSCs) are among the most common tumors worldwide. Despite the availability of various diagnostic and therapeutic strategies, the incidence and mortality rates of HNSC remain high. Cancer-associated fibroblasts (CAFs), as a major component of the tumor microenvironment, exhibit diverse biological characteristics in terms of origin, genetics, and phenotype, and have been increasingly recognized for their roles in tumor progression. Methods To investigate the potential role of CAFs in HNSC, we performed a comprehensive bioinformatics analysis based on the TCGA HNSC cohort. We applied single-sample gene set enrichment analysis (ssGSEA), single-cell RNA sequencing (scRNA-seq) analysis, differential expression analysis, Cox regression, LASSO regression, and pathway enrichment analysis to identify CAF-related genes and assess their prognostic value. Results We successfully identified a set of CAF-related genes and stratified the HNSC patients into high- and low-CAF groups. Based on the expression of these genes, we constructed a prognostic prediction model using LASSO and multivariate Cox regression analyses. A nomogram integrating the risk score and clinical characteristics was developed to improve individualized survival prediction. Enrichment analysis revealed that the type I interferon signaling pathway, cellular response to type I interferon, defense response to symbiont, and extracellular matrix organization were significantly associated with CAFs in HNSC. Conclusion Our study provides a novel CAF-based prognostic model and nomogram for predicting patient outcomes in HNSC. These findings highlight the importance of CAFs in the tumor microenvironment and their potential as therapeutic and prognostic biomarkers.
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spelling doaj-art-fa2cee10b1da4e62b798515476e63ed52025-08-20T03:48:19ZengSpringerDiscover Oncology2730-60112025-05-0116111410.1007/s12672-025-02507-1Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohortLing Zhong0Yixin Qiao1Shasha He2Yangju Fu3Jian Zou4Department of Anesthesiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan UniversityDepartment of Otolaryngology–Head & Neck Surgery, West China Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan UniversityDepartment of Otolaryngology–Head & Neck Surgery, West China Hospital, Sichuan UniversityAbstract Background Head and neck squamous cell carcinomas (HNSCs) are among the most common tumors worldwide. Despite the availability of various diagnostic and therapeutic strategies, the incidence and mortality rates of HNSC remain high. Cancer-associated fibroblasts (CAFs), as a major component of the tumor microenvironment, exhibit diverse biological characteristics in terms of origin, genetics, and phenotype, and have been increasingly recognized for their roles in tumor progression. Methods To investigate the potential role of CAFs in HNSC, we performed a comprehensive bioinformatics analysis based on the TCGA HNSC cohort. We applied single-sample gene set enrichment analysis (ssGSEA), single-cell RNA sequencing (scRNA-seq) analysis, differential expression analysis, Cox regression, LASSO regression, and pathway enrichment analysis to identify CAF-related genes and assess their prognostic value. Results We successfully identified a set of CAF-related genes and stratified the HNSC patients into high- and low-CAF groups. Based on the expression of these genes, we constructed a prognostic prediction model using LASSO and multivariate Cox regression analyses. A nomogram integrating the risk score and clinical characteristics was developed to improve individualized survival prediction. Enrichment analysis revealed that the type I interferon signaling pathway, cellular response to type I interferon, defense response to symbiont, and extracellular matrix organization were significantly associated with CAFs in HNSC. Conclusion Our study provides a novel CAF-based prognostic model and nomogram for predicting patient outcomes in HNSC. These findings highlight the importance of CAFs in the tumor microenvironment and their potential as therapeutic and prognostic biomarkers.https://doi.org/10.1007/s12672-025-02507-1Head and neck squamous cell carcinomaCancer-associated fibroblastImmune cell infiltrationSingle-cell RNA sequencing
spellingShingle Ling Zhong
Yixin Qiao
Shasha He
Yangju Fu
Jian Zou
Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
Discover Oncology
Head and neck squamous cell carcinoma
Cancer-associated fibroblast
Immune cell infiltration
Single-cell RNA sequencing
title Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
title_full Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
title_fullStr Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
title_full_unstemmed Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
title_short Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in head and neck squamous cell carcinomas cohort
title_sort single cell rna sequencing and traditional rna sequencing reveals the role of cancer associated fibroblasts in head and neck squamous cell carcinomas cohort
topic Head and neck squamous cell carcinoma
Cancer-associated fibroblast
Immune cell infiltration
Single-cell RNA sequencing
url https://doi.org/10.1007/s12672-025-02507-1
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