Development and validation of a TOP2A based index clinical model for kidney renal clear cell carcinoma

TOP2A (Topoisomerase II alpha) is significantly overexpressed in kidney renal clear cell carcinoma (KIRC), and its expression level is significantly associated with accelerated tumor progression and poor prognosis in patients. Therefore, the aim of this study is to systematically analyze the biological functions of TOP2A-related molecular markers in KIRC by constructing a TOP2A based index clinical model. Additionally, we aim to screen potential therapeutic targets to guide the optimization of clinical intervention strategies.

Integrated TCGA-KIRC data were standardized and analyzed via PCA. Differentially expressed genes between TOP2A high/low expression groups were screened and functionally annotated (GO/KEGG). WGCNA identified core TOP2A-associated modules, combined with Cox regression to construct a prognostic model. GSEA evaluated pathway activity, immune infiltration, and immune checkpoint correlations. Regulatory networks (miRNA/lncRNA/RBP), mutation profiles, and methylation-transcriptome interactions were explored.

5500 TOP2A-related deregulated genes were identified, with core modules enriched in cell cycle/DNA replication pathways. The TOP2A-index model inversely correlated with patient survival. High TOP2A expression scores showed positive associations with immune checkpoint genes. Multi-omics analyses revealed global regulatory networks linking TOP2A to tumor microenvironment modulation.

This study developed a TOP2A based index clinical model that will aid in predicting the prognosis of KIRC patients.