Overexpression of SIRT1 in urothelial carcinoma of the urinary bladder is associated with local recurrence and poor survival

Abstract

Objectives:To investigate the relationship of Silent mating type information regulation 2 homolog-1 (SIRT1) immunostaining to urothelial carcinoma of the urinary bladder (UCB) clinicopathological parameters.Methods:The study includes a total of 147 specimens composed of 122 urothelial carcinoma and 25 of non-neoplastic normal mucosae. The clinical information and the corresponding paraffin blocks of the cases were collected from the Pathology Department at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. Tissue microarrays were prepared and unstained slides were cut from the recipient blocks. Immunohistochemistry study was performed using anti-human SIRT1 antibody. The study was conducted from July 2016 until May 2018.Results:In UCB, high SIRT1 immunostaining (59.8%) was greater than low SIRT1 immunostaining (40.2%). High SIRT1 immunostaining was associated with local disease recurrence (p=0.017). However, there was no relation with other clinicopathological parameters. Regression analysis demonstrated that SIRT1 overexpression is an independent predictor of local disease recurrence (p=0.002). High SIRT1 immunostaining was associated with lower overall survival (log rank [Mantel-Cox]=6.478, and p=0.011) and disease-free survival (log rank [Mantel-Cox])=4.281, and p=0.039).Conclusion:The results revealed that SIRT1 is an important prognostic factor for UBC patients and is a potential target for therapeutic intervention. Further immunohistochemical and molecular evaluations are required to explore the mechanism of action of SIRT1 and to investigate molecular downstream of this potential biomarker in UCB.