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

Background: Mitochondrial permeability transition (MPT) driven necrosis may play a key role in the proliferation, death and spread of kidney renal clear cell carcinoma (KIRC). However, few studies have investigated key genes of MPT driven necrosis-related genes (MPTDNRGs) and KIRC using bioinformatics methods. Consequently, this study aims to create a precise prognostic tool for forecasting patient outcomes of KIRC patients. Methods: First, differentially expressed genes (DEGs) were acquired from KIRC and control samples in TCGA-KIRC dataset, as well as between high and low MPTDNRGs scores groups. Then, candidate MPTDNRGs were acquired by overlapping both DEGs. Next, key MPTDNRGs were obtained by Cox regression analysis. Subsequently, risk model and nomogram were constructed, along with enrichment analysis, immune analysis, and regulatory network were completed. Finally, the expression of key MPTDNRGs was validated clinically using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Three key MPTDNRGs, namely IL2RA , CD7 , and CXCL13 , were obtained to construct the risk model. The ROC analysis results showed that the AUC for 1 year, 3 years, and 5 years were 0.658, 0.614, and 0.625, respectively, indicating that the risk model has good effectiveness. Besides, risk score and age are independent prognostic factors. Next, we constructed a nomogram with a decent potential for clinical utility over risk score and age alone. Among the high-risk group, there was a significant concentration of pathways related to immune functions, particularly systemic lupus erythematosus, while the low-risk group was largely enriched in pathways associated with metabolic processes, such as butanoate metabolism. A sum of 25 immune cells exhibited significant differences from different risk groups, and high-risk group patients revealed significantly higher TIDE score, which indicated a higher likelihood of tumor immune escape in high risk group. Moreover, ceRNA network showed complex interaction pairs such as CXCL13 -hsa-miR-670-5p-AL121985.1, IL2RA -hsa-miR-6088-AL513497.1, and in total 25 TFs were predicted for key MPTDNRGs. Conclusion: In this study, three key genes ( IL2RA , CD7 and CXCL13 ) were integrated into a newly constructed prognostic model for KIRC, which offers clinicians a novel framework for more accurately forecasting patient outcomes and also presents a fresh target and approach for the management of KIRC.