Renal Tubular Epithelium in the Development of Renal Cell Carcinoma

Abstract

Objective: The objective of this study is to determine how dysregulations in developmental genes, transcription factors and signaling pathways of renal tubular epithelium contribute to Renal Cell Carcinoma development. Background: Renal Cell Carcinoma (RCC) presents a significant challenge in oncology due to its diverse clinical behaviors and inherent heterogeneity. Understanding its developmental dynamics is crucial for finding therapeutic opportunities. Key genes, TFs and signaling pathways, including PAX2, WT1, Wnt/β-catenin, and BMP, play key roles in RCC pathogenesis. This study aims to investigate RCC's origins and development, paving the way for possible effective, personalized interventions and improving patient outcomes. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate the key genetic architecture and developmental dynamics contributing to the development and origins of RCC. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate RCC oncogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study investigates the processes guiding Renal Cell Carcinoma (RCC) initiation. PAX2, WT1, RET, GATA3, HNF1B, OSR1 emerge as architects, controlling developmental dynamics. Transcription factors SIX2, HOXD11, EMX2 regulate renal stem/progenitor cell fate and enhance stemness, influencing RCC aggressiveness. Signaling pathways—Wnt/β-catenin, Notch, FGF, Shh, RAAS, BMP—act as regulators triggering epithelial-mesenchymal transition (EMT) and fostering angiogenesis. BMP and Wnt/β-catenin pathways drive EMT, enhancing stemness, key RCC drivers. NF-κB-mediated inflammation contributes to the immune microenvironment, potentially fueling RCC progression. These results point to the significance of investigating RCC through the lens of developmental dynamics. Conclusion: Renal Cell Carcinoma (RCC) originates from renal tubular epithelial cells, and understanding the developmental processes is crucial for finding its pathogenesis and origins. Genes like PAX2, WT1, RET, GATA3, HNF1B, OSR1, and transcription factors SIX2, HOXD11, EMX2, shape epithelial cell development in renal tubules. Signaling pathways such as Wnt/β-catenin, Notch, FGF, Hedgehog, RAAS, and BMP critically participate. Dysregulation in these key regulators, including BMP signaling disruption, may lead to a pathologic state, impacting cell fate, inflammation, and contributing to RCC development.