Abstract

We used our Genomic Fabric Therapy (GFT) approach to identify the transcriptomic consequences of clear cell renal cell carcinoma (ccRCC) on the genomic fabrics of five main pathways of the human excretory system: aldosterone-regulated sodium reabsorption (ALDO), collecting duct acid secretion (CDAS), proximal tubule bicarbonate reclamation (PTBR), mineral absorption (MABS), and vasopressin-regulated water reabsorption (VASO). The study was performed on deep RNA-seq data from paired tumor and non-tumor surrounding tissues from 72 ccRCC patients from the public Cancer Genome Atlas. ccRCC significantly altered the average expression level and expression control of a large majority of genes in each pathway, as well as the gene networks. We found that the tumor remodels the topologies and interactions of the excretory pathways to its own advantage. The GFT approach provides a comprehensive view of transcriptomic alterations that can guide the development of targeted therapies restoring normal pathway function.