# Comparative single‐cell transcriptomic profiling of patient‐derived renal carcinoma cells in cellular and animal models of kidney cancer

## TL;DR

This study compares different models of kidney cancer using a patient-derived cell line to understand how model systems affect gene expression and cancer progression.

## Contribution

The study introduces a comparative single-cell RNA-sequencing analysis of patient-derived ccRCC models to evaluate their similarity to human tumors.

## Key findings

- RCC243 tumors retained clear cell morphology across all models, including cell culture and metastatic mouse models.
- Gene expression profiles varied significantly between different RCC243 tumor models, highlighting the impact of the model system.
- Prognostic markers were conserved between RCC243 models and human ccRCC datasets, with metastatic gene upregulation linked to worse patient outcomes.

## Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer that often displays resistance to conventional cancer therapies, including chemotherapy and radiation therapy. Targeted treatments, including immunotherapies and small molecular inhibitors, have been associated with improved outcomes. However, variations in the patient response and the development of resistance suggest that more models that better recapitulate the pathogenesis and metastatic mechanisms of ccRCC are required to improve our understanding and disease management. Here, we examined the transcriptional landscapes of in vitro cell culture as well as in vivo orthotopic and metastatic NOD/SCID‐γ mouse models of ccRCC using a single patient‐derived RCC243 cell line to allow unambiguous comparison between models. In our mouse model assays, RCC243 cells formed metastatic tumors, and all tumors retained clear cell morphology irrespective of model type. Notably, gene expression profiles differed markedly between the RCC243 tumor models—cell culture, orthotopic tumors, and metastatic tumors—suggesting an impact of the experimental model system and whether the tumor was orthotopic or metastatic. Furthermore, we found conserved prognostic markers between RCC243 tumor models and human ccRCC patient datasets, and genes upregulated in metastatic RCC243 were associated with worse patient outcomes.

We generated and characterized clear cell renal cell carcinoma models using the patient‐derived RCC243 cell line—including cell culture, orthotopic, and metastatic tumors—via single‐cell RNA‐sequencing for comparisons between models and patient tumor datasets. RCC243 models were representative of human ccRCC that can be used to investigate kidney cancer progression and showed that the model system used impacts the gene expression profile.