[Retracted] Identification of a Ferroptosis‐Related Prognostic Signature in Sepsis via Bioinformatics Analyses and Experiment Validation

Abstract

Ferroptosis is a new type of programmed cell death that is different from apoptosis, cell necrosis, and autophagy, which might be involved in development of sepsis. However, the potential role of ferroptosis-related genes (FRGs) in sepsis remained unclear. We identified 41 ferroptosis-related differential expression genes by weighted correlation network and differential expression analysis. The hub module of 41 ferroptosis-related differential expression genes in the protein-protein interaction network was identified. Next, we estimated diagnostic values of genes in hub modules. TLR4, WIPI1, and GABARAPL2 with high diagnostic value were selected for construction of risk prognostic model. The high risk-scored patients had significantly higher mortality than the patients with low risk scores in discovery dataset. Furthermore, the risk scores of nonsurvivor were higher than those of survivor in validation dataset. It suggested that risk score was significantly correlated to prognosis in sepsis. Then, we constructed a nomogram for improving the clinical applicability of risk signature. Moreover, the risk score was significantly associated with immune infiltration in sepsis. Our comprehensive analysis of FRGs in sepsis demonstrated the potential roles in diagnosis, prognosis, and immune infiltration. This work may benefit in understanding FRGs in sepsis and pave a new path for diagnosis and assessment of prognosis.

Ferroptosis in Macrophage Impairment in Sepsis

“…Li et al [ 30 ] found that HIF-1 in myeloid cells α deletion can significantly reduce TNF- α expression of succinic acid and glutamine, as important intermediates of glucose metabolism, and can improve glucose metabolism in sepsis. Studies have shown that succinic acid and glutamine can directly or indirectly increase HIF-1 α level and stability and promote the production of inflammatory cytokines [ 31 ]. So far, the research on the effect of ferroptosis on succinic acid is not clear.…”

Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures

“…Based on the positive regulation of autophagy by WIPI1, quantifying the expression of WIPI1 mRNA or the number of WIPI1 puncta is considered a reliable method to assess the level of autophagosome formation ( Proikas-Cezanne et al, 2007 ; Tsuyuki et al, 2014 ). Consistent with our findings, in another bioinformatics study on ferroptosis-related genes, WIPI1 was found to be elevated in sepsis patients and correlated with patient outcomes ( Zhu et al, 2022 ).…”

A hypoxia- and lactate metabolism-related gene signature to predict prognosis of sepsis: discovery and validation in independent cohorts

“…This prognostic signature demonstrated good predictive performance for 28-day mortality in the internal and external validation datasets [ 27 ]. Zhu et al [ 36 ] identified a ferroptosis-related prognostic signature ( TLR4 , WIPI1 , and GABARAPL2 ), and Jiang et al [ 37 ] developed a signature consisting of nine inflammatory response-related genes ( CCL22 , CX3CL1 , CXCR6 , FFAR2 , FPR1 , HBEGF , ITGA5 , RGS16 , and SELL ) to predict prognosis. The AUC of the HLMRG signature was comparable to the AUCs of the signatures identified by the groups aforementioned, except that it was significantly higher than that of the signature identified by Zhu and his colleagues (0.674 vs. 0.599, P = 0.002; Fig.…”