PROGNOSTIC IMPLICATIONS OF ZIC1 EXPRESSION AND METHYLATION IN ORAL SQUAMOUS CELL CARCINOMA: INSIGHTS FOR ATHLETES

Abstract

Objective: Oral squamous cell carcinoma (OSCC) represents one of the most common malignancies of the head and neck, with a high incidence and an unfavorable prognosis owing to recurrence and metastasis. The development of OSCC involves genetic variations and epigenetic modification. In this study, we uncovered a differentially methylated gene (DMG) during the carcinogenesis of OSCC. Methods: The microarray dataset (GSE178216) was utilized to sort out DMGs between human OSCC tissues and matched control tissues. The retrospective study included tumor tissues and oral mucosal tissues from the cheek of the non-tumor side of 82 OSCC athletic patients who received primary surgical treatments for clinical validation of ZIC1 in relation to clinicopathological characteristics and recurrence-free survival (RFS) of OSCC. Results: A total of 117 DMGs with |log2FC| > 1 and P < 0.05 between OSCC tissues and matched control tissues were identified, among which ZIC1 was selected for clinical validation after the UALCAN database analysis. Results of qRT-PCR detection found that the mRNA expression of ZIC1 was declined in OSCC tissue samples compared to non-tumor oral mucosal tissues and this expression was associated with TNM classification. It was revealed that OSCC athletic patients with low ZIC1 expression exhibited reduced RFS compared to those with high ZIC1 expression. Multivariate logistic regression analysis showed an advanced TNM stage and a reduced mRNA expression of ZIC1 were independent risk factors of recurrence for OSCC athletic patients. Conclusion: These data support the notion that ZIC1 is downregulated and hypermethylated in OSCC and may be served as a tumor suppressor, providing a novel direction for epigenetic mechanisms underlying OSCC development.