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

## TL;DR

This study identifies five genes linked to mitochondrial necrosis that help predict outcomes for colorectal cancer patients and guide treatment choices.

## Contribution

The study identifies five MPTDN-related genes as novel prognostic markers for colorectal cancer.

## Key findings

- Five MPTDN-related genes (LMNB2, CASP7, PRKCB, GZMB, ENDOG) were identified as prognostic markers in CRC.
- High-risk patients had poor survival rates and elevated immune checkpoints.
- PRKCB and GZMB were highly expressed in stem cells, while LMNB2 was abundant in mast cells.

## Abstract

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

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.

The prognostic genes LMNB2, CASP7, PRKCB, GZMB and ENDOG 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 PRKCB and GZMB were highly expressed in stem cells, while LMNB2 was more abundantly expressed in mast cells. Real-time PCR (RT-qPCR) confirmed low levels of CASP7, PRKCB, and ENDOG mRNA in CRC tissues, with no significant difference between LMNB2 and GZMB.

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