Aarhus, Denmark (UroToday.com) Dr. Andrew Mason began this session by discussing their efforts at the University of York to molecularly characterize normal ureteric urothelium, in order to permit more meaningful comparisons with bladder urothelium. Donor-matched bladder and ureteric urothelial cells were obtained from five patients undergoing ureteral reimplantation for non-oncologic purposes, and these cells were cultured and re-differentiated in vitro.
mRNAseq urothelial transcriptomic data were generated to build tissue-specific signatures and then compared to the TCGA muscle-invasive bladder cancer (MIBC) cohort. Key findings included the lack of any nuclear receptors or transcription factors that drive urothelial differentiation and regulation between ureteric and bladder cells. Additionally, homeobox genes (which are top level regulators of cellular differentiation), were notably different between the bladder and ureteral cells. However, Dr. Mason noted that bladder homeobox signatures were not reproducible across the MIBC TCGA cohort, suggesting that dysregulation of cellular differentiation in part contributes to tumorigenesis.
Dr. Mason concluded that urinary tract (ureteral) and bladder urothelium share molecular similarities and ureteral tissue could serve as a control for studying bladder cancer. Additionally, homeobox gene dysregulation may play a role in the development of MIBC and warrants additional investigation.
Abstract take-home message:
- Ureteral and bladder urothelium share similar molecular characteristics, with homeobox dysregulation, potentially playing a role in the development of MIBC (based on TCGA MIBC comparisons)
Written by Dr. Vikram M. Narayan (@VikramNarayan), Urologic Oncology Fellow with Ashish M. Kamat, MD (@UroDocAsh), Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 17th meeting of the International Bladder Cancer Network, (IBCN, #IBCN2019) October 3rd – 5th, 2019 in Aarhus, Denmark.