Objective: Oral squamous cell carcinoma (OSCC) is a major global health concern, contributing significantly to cancer-related mortality. It arises from the mucosal lining of the oral cavity and is often preceded by potentially malignant lesions, such as leukoplakia and erythroplakia. Caspases, a family of proteases essential for apoptosis and inflammation, have gained prominence in cancer research. Among them, caspase-4, encoded by the CASP4 gene, plays a role in apoptosis induction and inflammatory responses, particularly through endoplasmic reticulum stress pathways. Material and Methods: This study aimed to evaluate caspase-4 messenger ribonucleic acid (mRNA) expression in OSCC and oral dysplastic lesions and investigate its association with the proliferation index, inflammation score, and apoptotic index. Clinical and histopathological data were documented, while immunohistochemical analysis was performed to assess Ki67 immunoexpression and apoptotic cell counts. Caspase-4 mRNA expression was quantified using real-time quantitative polymerase chain reaction. Results: A progressive downregulation of CASP4 expression was observed from normal tissue to dysplasia and OSCC. Notably, lower CASP4 expression was associated with OSCC progression, suggesting a potential tumor-suppressive function. However, no significant correlation was found between CASP4 expression and the proliferation index or inflammation score. Conclusion: These findings highlight the intricate relationship between apoptosis, inflammation, and tumorigenesis in OSCC. The observed downregulation of caspase-4 in OSCC suggests its potential as a prognostic biomarker and a marker for the malignant transformation of premalignant lesions. Further studies are warranted to elucidate the precise mechanistic role of CASP4 in OSCC pathogenesis.
TOKÖZLÜ et al. (2026) studied this question.