{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:06:33Z","timestamp":1785521193373,"version":"3.56.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"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><jats:title>Background<\/jats:title><jats:p>Sepsis, a life-threatening organ dysfunction caused by a dysregulated immune response to infection, remains a significant global health challenge. Phosphoglycerate kinase 1 (PGK1) has been implicated in regulating inflammation and immune cell infiltration in inflammatory conditions. However, the role of PGK1 in sepsis remains largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four microarray datasets and a high throughput sequencing dataset were acquired from GEO database to reveal the PGK1 expression in patients of sepsis. Quantitative real-time PCR and western blotting was then used to validate the PGK1 level. Additionally, microarray and single-cell RNA sequencing data integration, including gene set enrichment analysis (GSEA), KEGG and GO functional enrichment analysis, immune infiltration analysis, and single-cell sequencing analysis, were performed to elucidate the role of PGK1 in sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed a significant upregulation of PGK1 in sepsis patients, with the area under the ROC curve (AUC) exceeding 0.9 across multiple datasets, indicating PGK1\u2019s strong potential as a diagnostic biomarker. Notably, PGK1 was enriched in key immune-related pathways, including the TNF signaling pathways, and leukocyte transendothelial migration, suggesting its involvement in immune regulation. Furthermore, PGK1 expression showed a positive correlation with the levels of inflammatory mediators CXCL1, CXCL16, and the chemokine receptor CCR1. In terms of immune cell infiltration, PGK1 was positively correlated with naive B cells, resting memory CD4 T cell, gamma delta T cells, M0 macrophages, eosinophils and negatively correlated with plasma cells, CD8 T cells, activated memory CD4 T cell, Tregs, activated dendritic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study concluded that PGK1 served as a novel diagnostic biomarker for sepsis, with potential implications for prognosis and immune regulation. The significant upregulation of PGK1 in sepsis patients and its association with immune-related pathways and cell types highlight its potential role in the pathogenesis of sepsis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1449975","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T05:10:49Z","timestamp":1733461849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of PGK1 on immunoinfiltration by integrated single-cell and bulk RNA-sequencing analysis in sepsis"],"prefix":"10.3389","volume":"15","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoliang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingcheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yide","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kongyang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/aas.14045","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock in adults 2021 - endorsement by the Scandinavian society of anaesthesiology and intensive care medicine","volume":"66","author":"Rehn","year":"2022","journal-title":"Acta Anaesthesiol Scand"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","first-page":"103776","DOI":"10.1016\/j.ebiom.2021.103776","article-title":"Predicting sepsis severity at first clinical presentation: The role of endotypes and mechanistic signatures","volume":"75","author":"Baghela","year":"2022","journal-title":"Ebiomedicine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"103670","DOI":"10.1016\/j.ebiom.2021.103670","article-title":"Resolving immune cells with patrolling behaviour by magnetic resonance time-lapse single cell tracking","volume":"73","author":"Masthoff","year":"2021","journal-title":"Ebiomedicine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-022-01035-6","article-title":"Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cmi.2023.07.023","article-title":"Early-versus late-onset sepsis in neonates - time to shift the paradigm","volume":"30","author":"Russell","year":"2024","journal-title":"Clin Microbiol Infect"},{"key":"B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/cid\/cix254","article-title":"Mortality in severe human immunodeficiency virus-tuberculosis associates with innate immune activation and dysfunction of monocytes","volume":"65","author":"Janssen","year":"2017","journal-title":"Clin Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415236","article-title":"Systemic inflammatory response syndrome criteria in defining severe sepsis","volume":"372","author":"Kaukonen","year":"2015","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.319695","article-title":"Simultaneous targeting of IL-1-signaling and IL-6-trans-signaling preserves human pulmonary endothelial barrier function during a cytokine storm-brief report","volume":"43","author":"Colas-Algora","year":"2023","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s41419-019-1462-z","article-title":"Gpr174-deficient regulatory T cells decrease cytokine storm in septic mice","volume":"10","author":"Qiu","year":"2019","journal-title":"Cell Death Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7150\/thno.51756","article-title":"Neutrophil-derived trail is a proinflammatory subtype of neutrophil-derived extracellular vesicles","volume":"11","author":"Youn","year":"2021","journal-title":"Theranostics"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1257834","article-title":"A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection","volume":"14","author":"Qian","year":"2023","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01738","article-title":"Akt3-mediated protection against inflammatory demyelinating disease","volume":"10","author":"DuBois","year":"2019","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.05.014","article-title":"Antibacterial fusion protein BPI21\/LL-37 modification enhances the therapeutic efficacy of hUC-MSCs in sepsis","volume":"28","author":"Li","year":"2020","journal-title":"Mol Ther"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01391","article-title":"Extracellular vesicles from adipose tissue-derived stem cells affect notch-miR148a-3p axis to regulate polarization of macrophages and alleviate sepsis in mice","volume":"11","author":"Bai","year":"2020","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.05.012","article-title":"A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1 \u03b2 and IL-6","volume":"12","author":"Liao","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7150\/thno.37383","article-title":"Therapeutic targeting of YY1\/MZF1 axis by MZF1-uPEP inhibits aerobic glycolysis and neuroblastoma progression","volume":"10","author":"Fang","year":"2020","journal-title":"Theranostics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/s41467-019-13601-8","article-title":"O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth","volume":"11","author":"Nie","year":"2020","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13054-022-03893-6","article-title":"Immune effects of PI3K\/Akt\/HIF-1alpha-regulated glycolysis in polymorphonuclear neutrophils during sepsis","volume":"26","author":"Pan","year":"2022","journal-title":"Crit Care"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82587","article-title":"Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation","volume":"126","author":"Nguyen","year":"2016","journal-title":"J Clin Invest"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5228","DOI":"10.3390\/cancers14215228","article-title":"Prognosis and immunological characteristics of PGK1 in lung adenocarcinoma: A systematic analysis","volume":"14","author":"Yang","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.682461","article-title":"PGK1 is a key target for anti-glycolytic therapy of ovarian cancer: based on the comprehensive analysis of glycolysis-related genes","volume":"11","author":"Gou","year":"2021","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MA0721-825R","article-title":"Dynamic changes in human single-cell transcriptional signatures during fatal sepsis","volume":"110","author":"Qiu","year":"2021","journal-title":"J Leukoc Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7150\/thno.29545","article-title":"OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT\/mTOR signaling pathway in non-small cell lung cancer","volume":"9","author":"Li","year":"2019","journal-title":"Theranostics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.695420","article-title":"Expression characteristics and significant prognostic values of PGK1 in breast cancer","volume":"8","author":"Li","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"7711151","DOI":"10.1155\/2021\/7711151","article-title":"Systematic analysis uncovers associations of PGK1 with prognosis and immunological characteristics in breast cancer","volume":"2021","author":"Li","year":"2021","journal-title":"Dis Markers"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-016-0965-7","article-title":"PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis","volume":"65","author":"Zhao","year":"2016","journal-title":"Inflammation Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"114437","DOI":"10.1016\/j.biopha.2023.114437","article-title":"PGK1 modulates balance between pro- and anti-inflammatory cytokines by interacting with ITI-H4","volume":"161","author":"Park HB","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B29","doi-asserted-by":"publisher","first-page":"180289","DOI":"10.1038\/sdata.2018.289","article-title":"A protein-protein interaction map of the TNF-induced NF-kappaB signal transduction pathway","volume":"5","author":"Van Quickelberghe","year":"2018","journal-title":"Sci Data"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157837","article-title":"Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury","volume":"8","author":"Cross","year":"2023","journal-title":"JCI Insight"},{"key":"B31","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12964-019-0405-8","article-title":"Palmitoylation is required for TNF-R1 signaling","volume":"17","author":"Zingler","year":"2019","journal-title":"Cell Commun Signal"},{"key":"B32","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41420-023-01524-9","article-title":"The role of CXCL family members in different diseases","volume":"9","author":"Zhou","year":"2023","journal-title":"Cell Death Discovery"},{"key":"B33","doi-asserted-by":"publisher","first-page":"33123","DOI":"10.1038\/srep33123","article-title":"Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions","volume":"6","author":"Sawant","year":"2016","journal-title":"Sci Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/srep33123","article-title":"The role of proinflammatory cytokines and CXC chemokines (CXCL1-CXCL16) in the progression of prostate cancer: insights on their therapeutic management","volume":"29","author":"Ullah A","year":"2024","journal-title":"Cell Mol Biol Lett"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21813","article-title":"C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells","volume":"8","author":"Shin","year":"2017","journal-title":"Oncotarget"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ni1275","article-title":"Immune cell migration in inflammation: present and future therapeutic targets","volume":"6","author":"Luster","year":"2005","journal-title":"Nat Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399","article-title":"Neutrophil recruitment and function in health and inflammation","volume":"13","author":"Kolaczkowska","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"9247574","DOI":"10.1155\/2017\/9247574","article-title":"The many roles of galectin-3, a multifaceted molecule, in innate immune responses against pathogens","volume":"2017","author":"Diaz-Alvarez","year":"2017","journal-title":"Mediators Inflammation"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1163633","article-title":"The role of PD-1 signaling in health and immune-related diseases","volume":"14","author":"Chen","year":"2023","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad029","article-title":"Inhibition of phosphoglycerate kinase 1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism","volume":"119","author":"Lu","year":"2023","journal-title":"Cardiovasc Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0295-8","article-title":"Regulation of the innate immune system by autophagy: neutrophils, eosinophils, mast cells, NK cells","volume":"26","author":"Germic","year":"2019","journal-title":"Cell Death Differ"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01040-6","article-title":"A guide to adaptive immune memory","volume":"24","author":"Lam","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3390\/cells9030531","article-title":"Memory CD4(+) T cells in immunity and autoimmune diseases","volume":"9","author":"Raphael","year":"2020","journal-title":"Cells"},{"key":"B44","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.coche.2017.11.006","article-title":"CD8(+) T cells and NK cells: parallel and complementary soldiers of immunotherapy","volume":"19","author":"Rosenberg","year":"2018","journal-title":"Curr Opin Chem Eng"},{"key":"B45","doi-asserted-by":"publisher","first-page":"174835","DOI":"10.1016\/j.ejphar.2022.174835","article-title":"The basic functions of phosphoglycerate kinase 1 and its roles in cancer and other diseases","volume":"920","author":"Liu","year":"2022","journal-title":"Eur J Pharmacol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.3390\/molecules29061298","article-title":"The impact of glycolysis and its inhibitors on the immune response to inflammation and autoimmunity","volume":"29","author":"Pajak","year":"2024","journal-title":"Molecules"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0622-0","article-title":"A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling","volume":"562","author":"Bollong","year":"2018","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"116209","DOI":"10.1016\/j.ejmech.2024.116209","article-title":"Novel inhibitors targeting the PGK1 metabolic enzyme in glycolysis exhibit effective antitumor activity against kidney renal clear cell carcinoma in vitro and in vivo","volume":"267","author":"He","year":"2024","journal-title":"Eur J Med Chem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1449975\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T05:10:52Z","timestamp":1733461852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1449975\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2024.1449975"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1449975","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]},"article-number":"1449975"}}