EXPRESSION OF PIEZO1 IN CLEAR CELL RENAL CELL CARCINOMA: INSIGHTS FROM BIOINFORMATIC AND IMMUNOHISTOCHEMICAL ANALYSES

D. Jerka¹, P. Antosik², K. Bonowicz^1,3, D. Grzanka⁴, M. Gagat^1,3 | ¹Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland; ²Department of Dermatology and Venerology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland; ³Faculty of Medicine, Collegium Medicum, Mazovian Academy in Płock, Płock, Poland; ⁴Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland

Clear cell renal cell carcinoma (ccRCC) represents the predominant histological subtype of kidney cancer and is frequently linked to unfavorable clinical outcomes and resistance to conventional therapies¹. Due to the limited availability of validated prognostic markers, there is a pressing need to identify new molecular indicators that may support clinical stratification and treatment planning². Piezo1, a mechanosensitive ion channel involved in cellular mechanotransduction, has been associated with tumor progression in several malignancies, though its relevance in ccRCC remains insufficiently characterized³. The present study investigated the prognostic significance of PIEZO1 by analyzing its expression at both transcript and protein levels in ccRCC tissues and matched non-tumorous samples. Analysis of transcriptomic data from The Cancer Genome Atlas (TCGA) revealed a significant upregulation of PIEZO1 mRNA in tumor specimens (p<0.0001). Moreover, elevated transcript levels were strongly correlated with reduced overall survival (p<0.0001), suggesting a relationship with more aggressive disease phenotypes. Immunohistochemical (IHC) evaluation showed that PIEZO1 protein expression was generally lower in tumor tissue compared to adjacent normal tissue (p<0.0001). Interestingly, within the tumor group, cases exhibiting higher intratumoral PIEZO1 protein levels were significantly associated with poorer survival outcomes (p=0.0092), indicating its potential as an independent adverse prognostic factor. The results indicate dual PIEZO1 regulation in ccRCC, with mRNA upregulation and variable protein levels suggesting tumor-specific mechanisms. PIEZO1 may serve as a prognostic marker worth further study in precision oncology.