{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:12:31Z","timestamp":1793211151809,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis is a disease with high mortality caused by a dysregulated response to infection. Ferroptosis is a newly discovered type of cell death. Ferroptosis-related genes are involved in the occurrence and development of sepsis. However, research on the diagnostic value of ferroptosis-related protein biomarkers in sepsis serum is limited. This study aims to explore the clinical value of Ferroptosis-related proteins in diagnosing sepsis and predicting mortality risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A single-center, prospective, observational study was conducted from January to December 2023, involving 170 sepsis patients, 49 non-septic ICU patients, and 50 healthy individuals. Upon ICU admission, biochemical parameters, GCS, SOFA, and APACHE II scores were recorded, and surplus serum was stored at -80\u00b0C for biomarker analysis via ELISA. Diagnostic efficacy was evaluated using ROC curve analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline serum levels of ACSL4, GPX4, PTGS2, CL-11, IL-6, IL-8, PCT, and hs-CRP significantly differed among sepsis, non-septic, and healthy individuals (all p\n                      <jats:italic>-<\/jats:italic>\n                      value\n                      <jats:italic>&amp;lt;<\/jats:italic>\n                      0.01). ACSL4, GPX4, PTGS2, IL-6, IL-8, PCT, and hs-CRP demonstrated high diagnostic and differential diagnostic performance (AUC: 0.6688 to 0.9945). IL-10 and TNF-\u03b1 showed good diagnostic performance (AUC = 0.8955 and 0.7657, respectively). ACSL4 (AUC = 0.7127) was associated with predicting sepsis mortality. Serum levels of ACSL4, CL-11, and IL-6 above the cut-off value were associated with shorter survival times. ACSL4 levels were positively correlated with SOFA (Rho = 0.354, p\n                      <jats:italic>-<\/jats:italic>\n                      value &amp;lt; 0.0001), APACHE II (Rho = 0.317, p\n                      <jats:italic>-<\/jats:italic>\n                      value &amp;lt; 0.0001), and septic shock (Rho = 0.274, p\n                      <jats:italic>-<\/jats:italic>\n                      value = 0.003) scores but negatively correlated with the GCS score (Rho = -0.218, p\n                      <jats:italic>-<\/jats:italic>\n                      value = 0.018). GPX4 levels were positively correlated with SOFA (Rho = 0.204, p\n                      <jats:italic>-<\/jats:italic>\n                      value = 0.027) and APACHE II (Rho = 0.233, p\n                      <jats:italic>-<\/jats:italic>\n                      value = 0.011) scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ACSL4 and GPX4 have strong diagnostic and differential diagnostic value in sepsis, including the ability to predict 28-day mortality in sepsis patients, and may become new potential serum markers for the diagnostic and differential diagnostic of sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1528986","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:23:58Z","timestamp":1744071838000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Ferroptosis-related protein biomarkers for diagnosis, differential diagnosis, and short-term mortality in patients with sepsis in the intensive care unit"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhangrui","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41581-019-0199-3","article-title":"Prognostic and predictive enrichment in sepsis","volume":"16","author":"Stanski","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202311-2086SO","article-title":"From\u00a0ICU syndromes to ICU subphenotypes: consensus report and recommendations for developing precision medicine in the ICU","volume":"210","author":"Gordon","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1186\/s13054-020-02993-5","article-title":"Biomarkers of sepsis: time for a reappraisal","volume":"24","author":"Pierrakos","year":"2020","journal-title":"Crit Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.11.006","article-title":"When ferroptosis meets pathogenic infections","volume":"31","author":"Gao","year":"2023","journal-title":"Trends Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112910","article-title":"Enhancing insight into ferroptosis mechanisms in sepsis: A genomic and pharmacological approach integrating single-cell sequencing and Mendelian randomization","volume":"140","author":"Zhao","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2021.1072","article-title":"The emerging role of ferroptosis in sepsis","volume":"41","author":"Liu","year":"2022","journal-title":"DNA Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.956361","article-title":"Ferroptosis in sepsis: The mechanism, the role and the therapeutic potential","volume":"13","author":"Xl","year":"2022","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518","article-title":"Ferroptosis in infection, inflammation, and immunity","volume":"218","author":"Chen","year":"2021","journal-title":"J Exp Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16244","article-title":"Emerging roles of ferroptosis in infectious diseases","volume":"289","author":"Bagayoko","year":"2022","journal-title":"FEBS J"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1279","article-title":"Machine learning reveals ferroptosis features and a novel ferroptosis classifier in patients with sepsis","volume":"12","author":"Chen","year":"2024","journal-title":"Immun Inflammation Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112423","article-title":"The molecular mechanisms of ferroptosis and its role in cardiovascular disease","volume":"145","author":"Zhang","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13134","article-title":"D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2alpha-dependent manner","volume":"54","author":"Zhou","year":"2021","journal-title":"Cell Prolif"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00685-9","article-title":"Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer\u2019s disease","volume":"28","author":"Bao","year":"2021","journal-title":"Cell Death Differ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-020-00205-0","article-title":"Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis","volume":"25","author":"Liu","year":"2020","journal-title":"Cell Mol Biol Lett"},{"key":"B17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13045-019-0720-y","article-title":"Ferroptosis, a new form of cell death: opportunities and challenges in cancer","volume":"12","author":"Mou","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103417","article-title":"PRDM16 suppresses ferroptosis to protect against sepsis-associated acute kidney injury by targeting the NRF2\/GPX4 axis","volume":"78","author":"Zheng","year":"2024","journal-title":"Redox Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s42003-025-07531-z","article-title":"Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1\/GLS2 axis in sepsis-related acute lung injury","volume":"8","author":"Li","year":"2025","journal-title":"Commun Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.637162","article-title":"Characteristics and biomarkers of ferroptosis","volume":"9","author":"Chen","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7150\/thno.100080","article-title":"Ferroptosis at the nexus of metabolism and metabolic diseases","volume":"14","author":"Li","year":"2024","journal-title":"Theranostics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.08.124","article-title":"Identification of ACSL4 as a biomarker and contributor of ferroptosis","volume":"478","author":"Yuan","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103353","article-title":"Role of Hippo\/ACSL4 axis in ferroptosis-induced pericyte loss and vascular dysfunction in sepsis","volume":"78","author":"Liu","year":"2024","journal-title":"Redox Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20240524-00457","article-title":"Exploration of key ferroptosis-related genes as therapeutic targets for sepsis based on bioinformatics and the depiction of their immune profiles characterization","volume":"36","author":"Li","year":"2024","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20220727-00694","article-title":"Research progress of ferroptosis related pathways in sepsis","volume":"34","author":"Ma","year":"2022","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.903859","article-title":"Extracellular CIRP promotes GPX4-mediated ferroptosis in sepsis","volume":"13","author":"Shimizu","year":"2022","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.freeradbiomed.2024.11.007","article-title":"Ginsenoside Rb1 targets to HO-1 to improve sepsis by inhibiting ferroptosis","volume":"226","author":"He","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102655","article-title":"miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1\/Nrf2\/GPX4 in sepsis lung injury","volume":"62","author":"Shen","year":"2023","journal-title":"Redox Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.12.026","article-title":"Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation","volume":"24","author":"Liu","year":"2023","journal-title":"Bioact Mater"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114042","article-title":"Genetic analysis of diagnostic and therapeutic potential for ferroptosis in postoperative sepsis","volume":"147","author":"Pei","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.881914","article-title":"Diagnostic and predictive values of ferroptosis-related genes in child sepsis","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118356","article-title":"Curculigoside inhibits ferroptosis in ulcerative colitis through the induction of GPX4","volume":"259","author":"Wang","year":"2020","journal-title":"Life Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116512","article-title":"GPX4, ferroptosis, and diseases","volume":"174","author":"Zhang","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: molecular mechanisms\u00a0and\u00a0health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16059","article-title":"Signaling pathways and defense mechanisms of ferroptosis","volume":"289","author":"Liu","year":"2022","journal-title":"FEBS J"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat Chem Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsi.2019.10.058","article-title":"Identification, expression profile and analysis of the antimicrobial activity of collectin 11 (CL-11, CL-K1), a novel complement-associated pattern recognition molecule, in half-smooth tongue sole (Cynoglossus semilaevis)","volume":"95","author":"Huang","year":"2019","journal-title":"Fish Shellfish Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.01.010","article-title":"Complement related pattern recognition molecules as markers of short-term mortality\u00a0in intensive care patients","volume":"80","author":"Hansen","year":"2020","journal-title":"J Infect"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte chemoattractant protein-1 (MCP-1): an overview","volume":"29","author":"Deshmane","year":"2009","journal-title":"J Interferon Cytokine Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079804","article-title":"Central role for MCP-1\/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies","volume":"8","author":"Ziraldo","year":"2013","journal-title":"PloS One"},{"key":"B42","doi-asserted-by":"publisher","first-page":"R49","DOI":"10.1186\/cc5783","article-title":"Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis","volume":"11","author":"Bozza","year":"2007","journal-title":"Crit Care"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176781","article-title":"Association study of MCP-1 promoter polymorphisms with the susceptibility and progression of sepsis","volume":"12","author":"He","year":"2017","journal-title":"PloS One"},{"key":"B44","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.cytogfr.2018.12.004","article-title":"Recent advances in the biology of IL-1 family cytokines and their potential roles in development of sepsis","volume":"45","author":"Ge","year":"2019","journal-title":"Cytokine Growth Factor Rev"},{"key":"B45","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13054-019-2342-8","article-title":"A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome","volume":"23","author":"Flori","year":"2019","journal-title":"Crit Care"},{"key":"B46","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s13054-021-03622-5","article-title":"Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study","volume":"25","author":"Hausfater","year":"2021","journal-title":"Crit Care"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1528986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:24:05Z","timestamp":1744071845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1528986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1528986"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1528986","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]},"article-number":"1528986"}}