Dr Katims on the Feasibility of scRNA-seq in FGFR3+ Upper Tract Urothelial Carcinoma

Andrew Katims, MD, MPH, urologic oncology fellow, Memorial Sloan Kettering Cancer Center, discusses the feasibility of using single-cell RNA-sequencing (scRNA-seq) in FGFR3-mutated upper tract urothelial carcinoma.

At the 2023 American Urological Association Annual Meeting, Katims and colleagues presented findings from an investigation on the use of scRNA-seq to characterize the immune phenotype of FGFR3-mutated upper tract urothelial carcinoma. Using 7 individual tissue samples obtained from patients who were treatment naïve, researchers identified 19 immune cell clusters with unique biologic functions, including 8 T-cell clusters, which were categorized into FGFR3-mutated vs FGFR3 wild-type samples. FGFR-mutated disease had a T-cell phenotype characterized by a high frequency of active/exhausted Th17-like CD4 cells, lower levels of regulatory T cells, and increased amounts of CD8/cytotoxic cells in naïve state.

Although single-cell sequencing currently has a role in a research setting, it is not practical to use in a clinical setting at this point, Katims explains. He notes that several factors currently limit the practicality of scRNA-seq in a clinical setting, including its high cost.

However, the costs of bulk RNA sequencing are steadily falling, and results from bulk testing have been similar to those seen with scRNA-seq, Katims continues. Although scRNA-seq can provide a more granular picture, the targeted gene sequencing, followed by RNA sequencing, appear to be the current trajectory for testing patients with upper urothelial tract carcinoma, Katims notes. scRNA-seq could have a role; however, it will be important to validate these results in bulk RNA sequencing, which can be more affordable and have a more practical clinical application, Katims concludes.