The potential of mitochondrial permeability transition-driven necrosis-related genes in prognostic evaluation of colorectal cancer patients.

[BACKGROUND] Mitochondrial permeability transition-driven necrosis (MPTDN) has been implicated in a variety of diseases, but its relationship with colorectal cancer (CRC) prognosis is unclear.

[METHODS] In this study, TCGA-COAD and TCGA-READ datasets were analyzed to identify differentially expressed genes (DEGs) in CRCs. Differentially expressed MPTDNGRs (DE-MPTDNRGs) were identified by comparing DEGs to MPTDN-related genes (MPTDNRGs). Univariate Cox, Minimum Absolute Contraction and Selection Operator (LASSO) regression and risk scoring analysis divided TCGA-CRC patients into high- and low-risk cohorts.

[RESULTS] The prognostic genes , , , and were identified, and the survival rate of high-risk patients was poor. Independent prognostic factors, including risk score, age, and N stage, are effective predictors of survival. Immunoassays revealed that high-risk patients had 9 elevated immune checkpoints, while low-risk patients were more susceptible to pazopanib and temsirolimus. In addition, single-cell analysis showed that and were highly expressed in stem cells, while was more abundantly expressed in mast cells. Real-time PCR (RT-qPCR) confirmed low levels of , , and mRNA in CRC tissues, with no significant difference between and .

[CONCLUSION] These findings highlight 5 MPTDN-associated prognostic genes in CRC, providing insights for individualized treatment and prognosis.