Deciphering the clinical significance of Beclin-1 and Bcl-2 in urothelial carcinoma of bladder

ABSTRACT Background: Considering an important interplay of Beclin-1 and Bcl-2 in autophagy, where Bcl-2 inhibits autophagy by binding and inhibiting Beclin-1, evaluation of their expressions may provide insights into the tumor biology of the clinically distinct non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Materials and Methods: Beclin-1 and Bcl-2 expressions were examined by real-time quantitative polymerase chain reaction, Western hybridization, and immunohistochemical staining (IHC) in 47 NMIBC and 37 MIBC patients. Their expressions were evaluated in relation to patients’ demographics. Autophagic vesicles (AVs)/autophagy were examined by transmission electron microscopy (TEM). Results: Fold change expressions of Beclin-1 and Bcl-2, at the gene level, were observed to be asymmetrical/skewed. Significances of expressions at the mRNA level with tumor stage (P = 0.0415), grade (P = 0.0488), and size (0.0451) in the NMIBC cohort were observed, whereas Bcl-2 expression exhibited significances with stage (P = 0.0328) and tumor type (P = 0.0499) in NMIBC and MIBC (P = 0.0474) patients. Western blotting and IHC showed decreased Beclin-1 and increased Bcl-2 immunostaining with an increase in the tumor stage and grade. TEM micrographs recorded an increase in AVs/autophagy in a tumor stage and grade-dependent manner. Tumor size was identified as a predictor of short progression-free survival (P = 0.031) in NMIBC patients. The Kaplan–Meier test could not identify Beclin-1 and Bcl-2 as the predictors of survival outcomes. Conclusion: Beclin-1 downregulation, Bcl-2 upregulation, and increased autophagy in tumor stage and grade-dependent manner suggest their role in aggressiveness of the bladder cancer.