Introduction:
Sepsis is a leading cause of mortality in intensive care units worldwide. Ferroptosis, a form of regulated cell death dependent on iron, has been proven to be altered during sepsis, including increased iron transport and uptake into cells and decreased iron export. A better understanding of the role of ferroptosis in sepsis should expedite the identification of biomarkers for prognostic evaluation and therapeutic interventions.

Material and methods:
We used the mRNA expression profiles of sepsis patients from Gene Expression Omnibus (GEO) to analyze the expression level of ferroptosis-related genes and construct molecular subtypes.

Results:
Two distinct ferroptosis patterns were determined, and the overall survival of the two clusters was highly significantly different. Gene comparison analysis was performed on these two groups, and there were a total of 106 differentially expressed genes (DEGs). Pathway enrichment analysis of these genes showed that ferroptosis and immune-related pathways were enriched, suggesting that immune pathways might be critically involved in sepsis. To systematically predict the prognosis of sepsis, we constructed a nomogram model; the calibration plot nomogram showed excellent concordance for the 7-, 14-, and 28-day predicted and actual overall survival probabilities. Finally, the results of bioinformatics analysis were validated in animal and cell models.

Conclusions:
In this study, we construct a ferroptosis-related nomogram that can be used for prognostic prediction in sepsis. In addition, we revealed that ferroptosis played a non-negligible role in immune cell infiltration and guiding more effective immunotherapy strategies.