System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases

Abstract

Renal cell carcinoma (RCC) is a type of cancer that develops in the renal epithelium of the kidney. It is responsible for approximately 3% of adult malignancies, and 90-95% of neoplasms originate from the kidney. Advances in tumor diagnosis, innovative immune therapeutics, and checkpoint inhibitors-based treatment options improved the survival rate of patients with RCC accompanied by different risk factors. RCC Patients with diabetes, hepatitis C virus (HCV), or obesity (OB) may have a comorbidity, and finding the risk factor for better clinical treatment is an urgent issue. Therefore, the study focused on network-based gene expression analysis approaches to learning the impact of RCC on other comorbidities associated with the disease. The study found critical genetic factors and signal transduction pathways that share pathophysiology and commonly use dysregulated genes of the illness. Initially, the study identified 385 upregulated genes and 338 down-regulated genes involved with RCC. OB, chronic kidney disease (CKD), type 2 diabetes (T2D), and HCV significantly shared 28, 14, 5, and 3 genes, respectively. RCC shared one downregulated gene versican (VCAN) with OB and HCV and one downregulated gene oxidase homolog 2 (LOXL2) with OB and CKD. Interestingly, most of the shared pathways were linked with metabolism. The study also identified six prospective biomarkers, signaling pathways, and numerous critical regulatory and associated drug candidates for the disease. We believe that the discovery will help explain these diseases' complicated interplay and aid in developing novel therapeutic targets and drug candidates.

An Overview of Renal Cell Carcinoma Hallmarks, Drug Resistance, and Adjuvant Therapies

“…Approximately 80% of ccRCCs present inactivation of the Von Hoppel Lindau (VHL) gene by mutation or methylation (34,41). The VHL gene is a tumor suppressor and, in many cases, one of its alleles is inactivated by some kind of mutation, and the second is affected by a deletion in the 3p25-26 region in approximately 90% of cases of ccRCC (42)(43)(44), thereby playing an important role in both hereditary and sporadic disease (41). This mutation causes elevated levels of factors that induce hypoxia and increases the levels of vascular endothelial growth factor (VEGF), thereby facilitating tumor-associated angiogenesis.…”

Type Disparity in Sodium–Glucose Cotransporter-2 Inhibitors in Incidences of Renal Cell Carcinoma: A Propensity-Score-Matched Cohort Study

“…Diabetes is a risk factor for RCC, and poor outcomes have been observed in patients with type 2 diabetes (T2D) and comorbidity with RCC [ 1 , 2 , 3 ]. T2D and RCC have become a significant health burden and a concern in every country [ 4 ]. Therefore, decreasing the incidence of RCC in patients with T2D is crucial.…”