Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma.

Mitochondrial permeability transition (MPT)-driven necrosis is associated with kidney renal clear cell carcinoma (KIRC), but its role in prognosis remains unclear. This study develops a prognostic model for KIRC outcomes using MPT-driven necrosis-related genes (MPTDNRGs). Differentially expressed genes (DEGs) from TCGA-KIRC samples were analyzed and categorized based on MPTDNRGs scores. Three key genes-IL2RA, CD7, and CXCL13-were identified as significant prognostic markers and used to construct a risk model, validated through public datasets and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The risk score and age were the independent prognostic factors. A nomogram incorporating these factors demonstrated good clinical utility. The high-risk group was enriched in immune-related pathways, such as systemic lupus erythematosus, while the low-risk group showed enrichment in metabolism-related pathways, including butanoate metabolism. Significant differences in 25 immune cells were observed between the risk groups, with the high-risk group exhibiting higher TIDE scores, suggesting a greater likelihood of immune escape. Additionally, a ceRNA network revealed complex interactions, such as CXCL13-hsa-miR-670-5p-AL121985.1, and predicted 25 transcription factors for key MPTDNRGs. This study presents a novel prognostic model for KIRC based on three MPTDNRGs, offering valuable insights into KIRC prognosis and potential therapeutic targets.