The Genomic Fabrics of the Excretory System’s Functional Pathways Are Remodeled in Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically removed right kidney and its metastasis in the chest wall from the perspective of the Genomic Fabric Paradigm (GFP). GFP characterizes every single gene in each region by the independent variables: average expression level (AVE), relative expression variability (REV) and expression correlation (COR) with each other gene. While traditional approach is limited to only AVE analysis, the novel REV analysis indicates genes whose correct expression level is critical for cell survival and proliferation. COR analysis determines the real gene networks responsible for functional pathways. The analyses covered the pathways: aldosterone-regulated sodium reabsorption, collecting duct acid secretion, endocrine and other factor-regulated sodium reabsorption, proximal tubule bicarbonate reclamation, and vasopressin-regulated water reabsorption. The present study confirms the conclusion of our previously published articles on prostate and kidney cancers that even equally graded cancer nodules from the same tumor have different transcriptomic topologies. Therefore, the personalization of the anti-cancer therapy should go beyond the individual to his/her major cancer nodules.