Abstract 4017: Defining cell type-specific pathways in both cancer and tumor-microenvironment cells that impact survival of clear cell renal carcinoma patients

Abstract

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, with 5-year mortality of 25%. The molecular landscape of ccRCC has been elucidated by a number of next generation sequencing studies and complemented by recent global proteome and phosphoproteome results. However, a limitation of such studies is the mixture of signals from distinct cell populations, presenting challenges to subsequent interpretation. As a remedy, single nuclei RNA-seq (snRNA-seq) is able to dissect distinct cell populations and map their differential expression patterns. Using snRNA-seq from 30 ccRCC tumor samples, we identified distinct genetic pathways associated with survival in the TCGA patient cohort (525 patients) in multiple cell types, including immune and stromal components. Prognostic value of pathways was confirmed in an independent cohort with 130 patients. Multiple cancer cell-specific pathways were related to metabolism, suggesting that certain metabolites are less abundant in high-risk tumors. Using data from two independent large-scale metabolism ccRCC studies, we found metabolites’ levels changing in accordance with our predictions, when comparing low-risk to high-risk ccRCC tumors. Citation Format: Ilya Strunilin, Yige Wu, Ruiyang Liu, Wagma Caravan, Feng Chen, Li Ding. Defining cell type-specific pathways in both cancer and tumor-microenvironment cells that impact survival of clear cell renal carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4017.