CTTN, an actin-binding protein, is widely recognized for its role in promoting cancer progression. However, the CTTN genetic alterations and their mRNA expression associated with immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC) remain unclear.

This study aimed to investigate alterations in CTTN at the DNA, mRNA, and protein levels and evaluate its prognostic significance in overall survival and immunotherapy response in HNSCC.

Data from The Cancer Genome Atlas (TCGA)-HNSCC cohort were used to examine CTTN amplification and expression, along with their correlations to clinicopathological features. CTTN mRNA expression was validated in an independent cohort with HNSCC tissues and paired non-tumor tissues using real-time PCR. Kaplan-Meier survival analysis was conducted to evaluate patient prognosis, and the relationship between CTTN expression and response to PD-1/PD-L1 immunotherapy was assessed. Functional enrichment analysis was performed to explore biological pathways associated with CTTN.

CTTN is frequently amplified (27%) in HNSCC patients. CTTN expression was significantly upregulated in HNSCC tissues compared to non-tumor tissues, and elevated CTTN expression was associated with advanced clinicopathological features and poor survival. Furthermore, high CTTN expression was linked to resistance to PD-L1 immunotherapy. Functional enrichment analysis identified key pathways contributing to HNSCC development and progression.

CTTN amplification and upregulation may serve as a predictive biomarker for poor prognosis and immunotherapy resistance in HNSCC patients. Further studies are warranted to elucidate the underlying mechanisms and validate its potential as a therapeutic target.