Identification of WIPI1 as A Potential Ferroptosis-Related Biomarker in Sepsis and Validation in CLP Mice Model.

Background: Sepsis is the leading cause of death and critical illness worldwide. Ferroptosis is a new type of programmed cell death that is different from apoptosis, cell necrosis, and autophagy, which might contribute to development of sepsis. However, it lacks of a rapid, accurate diagnostic method and a therapeutic target of sepsis. In this work, we identified a novel promising biomarker related to ferroptosis in sepsis.MethodsThe expression profiles of mRNAs were downloaded from Gene Expression Omnibus (GEO) database, and ferroptosis-related genes were used to screen differential genes. Furthermore, we identified potential ferroptosis-related biomarkers through a series of comprehensive bioinformatics analysis, such as differential analysis, enrichment analysis, protein-protein interactions (PPI). Moreover, the receiver operating characteristic (ROC) was used to evaluate the diagnostic value of biomarkers and the relative expressions of biomarker were measured by quantitative real-time PCR (qRT-PCR) in cecum ligation and puncture (CLP) mice model. Finally, immune infiltration analysis was preformed to explore the relationship between ferroptosis-related biomarkers and immune regulation. ResultsTotally 52 (36 upregulated and 16 downregulated) overlapped ferroptosis-related differential expression genes differentially expressed genes (FRDEGs) from two GEO datasets were identified between sepsis and normal samples. Upregulated ferroptosis-related WD Repeat Domain, Phosphoinositide Interacting 1 (WIPI1), with high area under curve (AUC) was selected as a promising biomarker, according to expression of WIPI1, septic samples were divided into high-expression and low-expression group. There are significant differences in the infiltration of some immune cells between the two group. ConclusionIn summary, we identified WIPI1 as a novel biomarker that may involve in immune regulation of sepsis by ferroptosis. In addition, this work contributes to the rapid, accurate and convenient diagnosis of sepsis.