# Bioinformatics-based screening and validation of ferroptosis-related genes in sepsis and type 2 diabetes mellitus

## TL;DR

This study explores how sepsis and type 2 diabetes interact through ferroptosis-related genes, identifying key genes and potential drugs for treatment.

## Contribution

The study identifies five core ferroptosis-related genes and eight candidate drugs for sepsis-T2DM comorbidity.

## Key findings

- Three signaling pathways (MAPK, adherens junction, and peroxisome) are significantly linked to sepsis-T2DM comorbidity.
- Five core ferroptosis-related genes (CDC25B, DPP7, FBXO31, PTCD3, CNPY2) were identified and validated.
- Echinacea and Ibudilast were predicted to have the greatest preclinical potential for targeting these genes.

## Abstract

Emerging clinical evidence underscores a bidirectional epidemiological linkage between sepsis and type 2 diabetes mellitus (T2DM). This study mechanistically investigates the underlying pathogenesis of this comorbidity, specifically focusing on the role of ferroptosis-related genes in its pathogenesis. A total of 1204 shared genes between sepsis and T2DM were screened using datasets from sepsis (GSE65682) and T2DM (GSE76894). GO and KEGG enrichment analyses, combined with WGCNA, were performed to identify key pathways and hub genes. Three signaling pathways—MAPK, adherens junction, and peroxisome—were significantly associated with the sepsis-T2DM interaction. Subsequent Pearson correlation analysis implicated ferroptosis as a critically involved process. Five core ferroptosis-related genes, including CDC25B, DPP7, FBXO31, PTCD3, and CNPY2, were were identified and experimentally validated using qRT-PCR. Furthermore, based on cMAP, we screened eight candidate drugs targeting these genes. Echinacea and Ibudilast were predicted to possess the greatest preclinical potential among them. This study provides a deeper insight into the shared pathogenesis of sepsis and T2DM, highlighting the pivotal role of ferroptosis in the development and progression of this comorbidity. Our findings offer preliminary insights into the sepsis-T2DM comorbidity, highlighting ferroptosis as a potential key pathological mechanism and identifying candidate targets for future therapeutic exploration.