TMEM92 drives EMT-associated invasiveness, cisplatin resistance, and immune suppression in head and neck squamous cell carcinoma.

Transmembrane protein 92 (TMEM92) has been implicated in tumor progression in several malignancies, yet its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, we systematically investigated the expression pattern, clinical relevance, and biological functions of TMEM92 in HNSCC. Transcriptomic and clinical data from TCGA and GEO were analysed, including bulk, single-cell, and spatial transcriptomic data from GEO. TMEM92 was significantly upregulated in HNSCC, particularly in HPV-negative tumors, and high TMEM92 expression was independently associated with poor overall survival. Single-cell analysis revealed that TMEM92 expression was predominantly enriched in malignant cells. Functional analyses and in vitro experiments demonstrated that TMEM92 promoted cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and cisplatin resistance. Moreover, elevated TMEM92 expression was associated with lymph node metastasis, an immunosuppressive tumor microenvironment, and a poor predicted response to immunotherapy. These findings suggest that TMEM92 plays a critical role in HNSCC progression and may serve as a potential prognostic biomarker and therapeutic target.