[Preliminary study on immune infiltration characteristics and prognostic value of the ferroptosis suppressor CAV1 in head and neck squamous cell carcinoma].

Authors

G L Liu, H Zhang, R Wang, F R Yang, H K Sun, R X Shi, F Yang

Published in

Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology. Volume 61. Issue 11. Pages 1649-1655. Nov 05, 2026. Epub Nov 05, 2026.

Abstract

Objective: To identify key ferroptosis suppressor genes in head and neck squamous cell carcinoma (HNSCC), and to comprehensively analyze their expression patterns, prognostic value, immune infiltration characteristics, and preliminary biological functions. Methods: Ferroptosis suppressor genes were obtained from the FerrDb database, and the HNSCC cohort from The Cancer Genome Atlas (TCGA) was used to evaluate their expression profiles. Kaplan-Meier survival analysis was performed to determine the prognostic value of ferroptosis suppressor genes. Immune infiltration analysis, immune checkpoint correlation analysis, and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to assess the immune microenvironment and predicted response to immunotherapy. In addition, GSE181919 single-cell data, immunohistochemistry, Western blotting, and in vitro functional experiments were used to preliminarily validate the cellular source, expression, and biological role of CAV1. Results: Forty-eight ferroptosis suppressor genes were retrieved from FerrDb, and 10 differentially expressed genes were identified in the TCGA HNSCC cohort. Among them, CAV1 was significantly upregulated. High CAV1 expression was associated with poorer overall survival and disease-specific survival in patients with HNSCC (P=0.009 and P=0.021, respectively). Immune analysis showed that high CAV1 expression was associated with reduced CD8+T-cell infiltration, increased expression of immune checkpoint-related genes, and a poorer predicted response to immunotherapy. External validation using the GSE25099 dataset further confirmed that CAV1 expression was significantly higher in oral squamous cell carcinoma tissues than in normal tissues (P<0.000 1). Single-cell analysis of GSE181919 showed that CAV1 was mainly detected in malignant cells, fibroblasts, and endothelial cells, and CAV1-high malignant cells exhibited enhanced potential immunosuppressive communication. Joint TCGA analysis showed that the CAV1-high/ferroptosis-resistance-high subgroup had the lowest CD8+T-cell infiltration. Immunohistochemistry also showed increased CAV1 expression in oral squamous cell carcinoma tissues. Western blotting confirmed endogenous CAV1 protein expression in CAL27 cells and effective CAV1 knockdown after siCAV1 transfection. In vitro experiments demonstrated that CAV1 knockdown significantly inhibited migration and proliferation of CAL27 cells (both P<0.01) and reduced colony formation ability (P<0.001). Conclusions: CAV1 may serve as a potential prognostic biomarker in HNSCC and is associated with an immunosuppressive tumor microenvironment. Preliminary experimental findings further support a tumor-promoting role of CAV1 in oral squamous cell carcinoma, whereas the causal mechanisms linking CAV1 to immune infiltration and ferroptosis resistance require further validation.

PMID:
43000842
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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