Association of higher transient receptor potential melastatin 8 expression with higher tumor histologic grades, lymph node metastasis, risk factors, and worse survival in patients with head and neck squamous cell carcinoma

Background/purpose: Transient receptor potential melastatin 8 (TRPM8), a thermosensitive ion channel known for its role in cold sensation and menthol response, has emerged as a potential regulator in various cancers. This study aimed to investigate expression trends of TRPM8 in head and neck squamous cell carcinoma (HNSCC) cases and oral squamous cell carcinoma (OSCC) cell lines and its association with clinicopathological features. Materials and methods: The noncancerous matched tissues and HNSCC paired tissue samples from 84 HNSCC patients were utilized to evaluate the association of TRPM8 with HNSCC clinicopathological features. TRPM8 expression was examined in HNSCC patient tissues and OSCC cell lines treated with arecoline. Results: Kaplan-Meier survival analysis of TCGA data revealed high TRPM8 expression correlated with unfavorable outcomes and higher tumor histologic grades. TRPM8 mRNA expression was upregulated in HNSCC cell lines and patients’ tissue samples. Arecoline treatment led to significantly increased TRPM8 mRNA and protein expression in OSCC cell lines. Lymph node metastasis showed a significant association with upregulated TRPM8 expression in combined OSCC and oropharyngeal squamous cell carcinoma (OPSCC) cases. TRPM8 mRNA expression was upregulated in HNSCC and OSCC patients with alcohol drinking and cigarette smoking habits, but not in betel quid chewing. Conclusion: These findings reveal the involvement of TRPM8 in HNSCC's malignant development and metastasis, suggesting that high expression of TRMP8 may be mutually causal with addiction to tobacco, alcohol, and betel nut in HNSCC patients. Further investigations are needed to determine the underlying pathways of TRPM8 in HNSCC's development and progression.