Unravelling the complexity of kidney renal clear cell carcinoma prognosis: integrating chromatin regulators, gene signatures and associated immune landscapes

Abstract

Abstract Background Kidney-renal clear cell carcinoma (KIRC) is the main subtype of renal cell carcinoma. KIRC exhibits significant resistance to conventional treatments, highlighting the need for pioneering therapeutic approaches. Within this framework, chromatin regulators (CRs) - proteins important for managing gene expression and orchestrating key biological processes - have been recognized as key players in the initiation and development of KIRC. Methods Utilizing the TCGA-KIRC dataset, we conducted differential gene analysis pertaining to chromatin regulators through application of the "limma" R package. We proceeded to establish and validate a prognostic model via LASSO Cox regression, with a particular emphasis on genes exerting substantial influence on KIRC prognosis. Our investigation was further extended to investigate the interrelationship between gene attributes, clinical parameters, the tumor microenvironment, and drug responsiveness. To enhance the predictive efficacy of our models, we harnessed advanced bioinformatics methodologies and techniques for visualizing protein interaction networks. Results Through the related studies, we found that the risk score obtained for CRs constituted an autonomous prognostic determinant in KIRC. Subsequently, a Nomogram prediction model was crafted that amalgamated clinical attributes with their corresponding risk evaluations. Ultimately, Polymerase chain reaction (PCR) was applied for comparative analysis of BRD9 expression levels in normal tissues and tumor specimens. Notably, the utilization of BRD9 marker-based constructs yielded significant predictive results. Conclusion We have introduced a novel prognostic framework for KIRC that seamlessly incorporates Chromatin Regulators. This innovative model exhibits substantial promise in enhancing the precision of prognostic forecasts for individuals afflicted with KIRC, thereby establishing a foundational platform for the refinement of therapeutic approaches.