Computational multi-omics modelling identifies TOP2A as a central prognostic biomarker and therapeutic target in renal cell carcinoma.

This study systematically investigates the clinicopathological and molecular significance and tumorigenic functions of TOP2A in the kidney cancer subtypes KIRC, KIRP, and KICH through integrative bioinformatics analyses utilizing TCGA and a suite of different databases, including cBioPortal, UALCAN, GEPIA, TIMER, KM Plotter, TISIDB, OncoDB, ENCORI, MEXPRESS, String, GeneMANIA, and the Human Protein Atlas etc. TOP2A expression was found to be significantly upregulated across a range of clinical contexts, including pathological stage, histological subtype, tumor grade, and lymph node involvement. Aggressive tumor characteristics and poor patient outcomes were consistently linked to elevated TOP2A levels. Frequent changes at the TOP2A locus were found by genomic profiling, primarily in the form of gene amplifications and mutations. Correlation analysis corroborated TOP2A involvement in abnormal cell cycle regulation by showing a strong positive association between TOP2A and CDK family members. TOP2A expression is strongly correlated to various immune cell types and immunomodulatory variables, according to additional investigation of immune infiltration, suggesting a potential role in forming the tumor immune microenvironment. Furthermore, pathway enrichment analysis revealed that TOP2A expression levels influence the activation or suppression of multiple cancer-related signaling pathways. Higher TOP2A expression is associated with enhanced sensitivity to certain anticancer treatments, according to drug sensitivity analysis based on GDSC data and Pearson correlation. Furthermore, the notion that TOP2A plays a key role in oncogenic networks was supported by protein-protein interaction network analysis. Overall, these findings imply that TOP2A may be a possible therapeutic target in KIRC, KIRP, and KICH as well as a helpful predictive biomarker.