Expression of ALDH1 isotypes and its potential as a prognostic and diagnostic marker in patients with muscle invasive bladder cancer.

ALDH1 isotype is an established cancer stem cell marker. In this study, immunohistochemical (IHC) expression of ALDH1/2 and ALDH1A3 protein was evaluated in a retrospective cohort of 99 pathologically confirmed MIBC patients and 11 distant normal bladder urothelium. IHC expression was assessed quantitatively using histopathology score (H score). H score of  ≥ 4 was graded as a high expression. Gene expression of ALDH1A1, 1A2 and 1A3 along with immunoblot procedure was also performed in a prospectively collected 30 MIBC patients to further validate the IHC findings. Expression of both ALDH1/2 and ALDH1A3 were found to be significantly higher in MIBC tumors than in the normal bladder urothelium. Tumors with higher T stage showed a significant association with ALDH1A3 expression (p = 0.002). Patients with a high H score of ALDH1A3 protein survived for significantly less (p = 0.008) duration of time (20 months) than patients with low score (34 months). Gene expression profile of ALDH1 isotypes revealed that high mRNA expression of ALDH1A3 was significantly associated with less overall survival which was further validated separately using public dataset. Our results indicate that ALDH1 isotypes have the potential to be used as an effective diagnostic and prognostic marker in patients with MIBC.