33P - Unraveling the mechanisms of cisplatin resistance in bladder organoid by single cell RNA sequencing

Background

Bladder cancer is a globally recognized malignancy for its high recurrence and progression rates. The primary treatment protocol involves cisplatin-based chemotherapy, however, the emergence of cisplatin resistance significantly impedes successful treatment outcomes. In this study, we utilized organoids, a 3D culture model, derived from patient bladder tumors to explore the molecular mechanisms underlying cisplatin resistance.

Methods

To dissect the complex cellular and molecular heterogeneity that fuels cisplatin resistance in bladder cancer, we employed single-cell RNA sequencing (scRNA-seq) technology which enable us to achieve high-resolution characterization of cisplatin-resistant cell populations and their unique gene expression profiles.

Results

We successfully induced two cisplatin resistance bladder cancer patient-derived organoids (PDOs). Through the application of scRNA-seq, we were able to generate exhaustive transcriptomic profiles of individual cells within cisplatin-resistant bladder cancer PDOs. This enabled us to identify specific gene expression patterns linked to resistance. This high-resolution analysis will reveal rare or previously unidentified cell subpopulations that are instrumental in driving cisplatin resistance.

Conclusions

In conclusion, this study signifies a pioneering effort to employ scRNA-seq technology and PDOs to unravel the cellular and molecular mechanisms that govern cisplatin resistance. Comprehensive transcriptomic analysis and integrative studies shed light on the complex biology of resistance and will suggest novel treatment approaches. Ultimately, our research aims to transform the management of cisplatin-resistant bladder cancer, bringing us a step closer to personalized and effective treatment strategies for enhanced patient outcomes.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

CUHK Direct grant.

Disclosure

All authors have declared no conflicts of interest.