Abstract
BACKGROUND: In search of salivary biomarkers for Head Neck Squamous Cell Carcinoma (HNSCC), we found Cornulin to be the most downregulated(~10-fold) protein during our previous study, which identified 135 dysregulated proteins in the saliva of the patients. The current study aimed to explore the role(s) of Cornulin in pathophysiology of HNSCC and its translational application. METHODS: The sandwich ELISA and immunohistochemistry assessed the levels of Cornulin in the saliva and primary tumour tissues, respectively, in a cohort of 128 HNSCC patients. The effects of Cornulin modulation were evaluated in-vitro and in-vivo HNSCC models and associated mechanisms were explored by analysis of transcriptomic and proteomic signatures. RESULTS: Cornulin was significantly downregulated in saliva and tumour tissue, which was also associated with tumour differentiation and poor survival. Cell proliferation, migration, viability, and invasion were decreased in Cornulin overexpressed HNSCC cell lines, which was substantiated using in-vivo model, suggesting the anti-tumour role of Cornulin. We identified the probable mechanism through cell cycle arrest in the G1 phase by upregulating p18 and reducing the free intracellular calcium. CONCLUSION: In conclusion, we report the multifaceted roles of Cornulin in HNSCC, as a potential prognostic biomarker with anti-tumour properties.