{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:34:50Z","timestamp":1792816490722,"version":"4.5.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background and aim<\/jats:title><jats:p>Traumatic brain injury (TBI) poses a significant burden on the global economy due to its poor treatment and prognosis. Current TBI markers do not comprehensively reflect the disease status. Therefore, identifying more meaningful biomarkers is beneficial for improving the prognosis and clinical treatment of TBI patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gene expression profile of TBI was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were subjected to enrichment analysis, and key potential genes were identified through the protein\u2013protein interaction network and cytoHubba modules. ROC curves were used to construct diagnostic models for hub genes. Immunofluorescence experiments were conducted to detect the expression of candidate biomarkers in TBI rat models. Finally, we investigated the expression of TBI biomarkers in normal human organs and pan-cancer tumor tissues, and evaluated their correlation with immune infiltration in different tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 44 DEGs were identified across four brain regions of TBI patients. Enrichment analysis revealed that these genes were primarily involved in intracellular and cell signal transduction pathways. Furthermore, three hub genes- RPS4Y1, KDM5D and NLGN4Y-were identified through different module analysis. The ROC curve diagnostic model also confirmed that these genes also have high diagnostic value in serum. Subsequently, the presence of Kdm5d was detected in the brain tissue of TBI rats through immunofluorescence experiments. Compared to normal rats, Kdm5d expression increased in the cortical area of \u200b\u200bTBI rats, with no significant change in the hippocampus area, aligning with observations in TBI patients. Immune infiltration analysis demonstrated changes in immune cell subsets in HIP and PCx, revealing that plasma cells and CD8 T cells were lowly expressed in TBI (HIP) and while neutrophils was under-expressed in TBI (PCx). Pan-cancer analysis indicated that KDM5D was significantly up-regulated in 23 cancers, down-regulated in 3 cancers, and significantly associated with immune infiltration in 10 cancers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on the results of bioinformatics analysis and animal experiments, KDM5D serves as a potential biomarker for the diagnosis and prognosis of TBI. Additionally, research on KDM5D may develop into new serum markers, providing new indicators for further clinical liquid biopsy and aiding in the prevention of both TBI and tumors to a certain extent.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1538561","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T09:23:55Z","timestamp":1742808235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Discovery of KDM5D as a novel biomarker for traumatic brain injury identified through bioinformatics analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Dengfeng","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhe","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinou","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0676-1_6","article-title":"Decompressive craniectomy - operative technique and perioperative care","volume":"38","author":"Timofeev","year":"2012","journal-title":"Adv Tech Stand Neurosurg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09541-4","article-title":"Recent advances in traumatic brain injury","volume":"266","author":"Khellaf","year":"2019","journal-title":"J Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6974257","DOI":"10.1155\/2016\/6974257","article-title":"Oxidation-reduction potential as a biomarker for severity and acute outcome in traumatic brain injury","volume":"2016","author":"Bjugstad","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/emermed-2013-203488","article-title":"Glasgow Coma Scale is unreliable for the prediction of severe head injury in elderly trauma patients","volume":"32","author":"Kehoe","year":"2015","journal-title":"Emerg Med J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(74)91639-0","article-title":"Assessment of coma and impaired consciousness. A practical scale","volume":"2","author":"Teasdale","year":"1974","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jns.2005.09.007","article-title":"Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome","volume":"240","author":"Nyl\u00e9n","year":"2006","journal-title":"J Neurol Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/jnr.23503","article-title":"A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury","volume":"93","author":"Yu","year":"2015","journal-title":"J Neurosci Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2004.21.1553","article-title":"GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome","volume":"21","author":"Pelinka","year":"2004","journal-title":"J Neurotrauma"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2008.12.022","article-title":"Tau proteins in serum predict outcome after severe traumatic brain injury","volume":"160","author":"Liliang","year":"2010","journal-title":"J Surg Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-008-1056-1","article-title":"Moderate and severe traumatic brain injury induce early overexpression of systemic and brain gelatinases","volume":"34","author":"Vilalta","year":"2008","journal-title":"Intensive Care Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181b788ab","article-title":"Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury","volume":"38","author":"Papa","year":"2010","journal-title":"Crit Care Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s12964-019-0406-7","article-title":"NFAT5 mediates hypertonic stress-induced atherosclerosis via activating NLRP3 inflammasome in endothelium","volume":"17","author":"Ma","year":"2019","journal-title":"Cell Commun Signal"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318299616a","article-title":"Traumatic brain injury-induced alterations in peripheral immunity","volume":"75","author":"Schwulst","year":"2013","journal-title":"J Trauma Acute Care Surg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-191150","article-title":"Inflammation in traumatic brain injury","volume":"74","author":"Postolache","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2022-002246","article-title":"Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events","volume":"9","author":"Lin","year":"2024","journal-title":"Stroke Vasc Neurol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00702","article-title":"Cytoscape stringApp: network analysis and visualization of proteomics data","volume":"18","author":"Doncheva","year":"2019","journal-title":"J Proteome Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"tkae004","DOI":"10.1093\/burnst\/tkae004","article-title":"Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury","volume":"12","author":"Liu","year":"2024","journal-title":"Burns Trauma"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.993955","article-title":"Glutamatergic and GABAergic neurons in the preoptic area of the hypothalamus play key roles in menopausal hot flashes","volume":"14","author":"Sun","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12412","article-title":"Identification of novel genes associated with atherosclerosis in Bama miniature pig","volume":"7","author":"Ding","year":"2024","journal-title":"Anim Model Exp Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174108","article-title":"Perineuronal nets and their role in synaptic homeostasis","volume":"20","author":"Bosiacki","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e14702","DOI":"10.1111\/cns.14702","article-title":"Molecular mechanism analyses of post-traumatic epilepsy and hereditary epilepsy based on 10\u00d7 single-cell transcriptome sequencing technology","volume":"30","author":"Wen","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic brain injury: progress and challenges in prevention, clinical care, and research","volume":"21","author":"Maas","year":"2022","journal-title":"Lancet Neurol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12964-023-01387-8","article-title":"Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"22","author":"Wei","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1177\/1076029619895111","article-title":"Effect of hydroxyurea treatment on the inflammatory markers among children with sickle cell disease","volume":"26","author":"Zahran","year":"2020","journal-title":"Clin Appl Thromb Hemost"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.949573","article-title":"Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice","volume":"15","author":"Cheng","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.07.039","article-title":"A review of the molecular mechanisms of traumatic brain injury","volume":"131","author":"Ladak","year":"2019","journal-title":"World Neurosurg"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.14670\/HH-17.1137","article-title":"Molecular mechanisms in the pathogenesis of traumatic brain injury","volume":"17","author":"Ray","year":"2002","journal-title":"Histol Histopathol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X16666180911121847","article-title":"Traumatic brain injury altered normal brain signaling pathways: implications for novel therapeutics approaches","volume":"17","author":"Rana","year":"2019","journal-title":"Curr Neuropharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10250","article-title":"Dysregulated expression of RPS4Y1 (ribosomal protein S4, Y-linked 1) impairs STAT3 (signal transducer and activator of transcription 3) signaling to suppress trophoblast cell migration and invasion in preeclampsia","volume":"71","author":"Chen","year":"2018","journal-title":"Hypertension"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S329209","article-title":"RPS4Y1 promotes high glucose-induced endothelial cell apoptosis and inflammation by activation of the p38 MAPK signaling","volume":"14","author":"Chen","year":"2021","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"102465","DOI":"10.1016\/j.jaut.2020.102465","article-title":"Identification of Ribosomal Protein S4, Y-Linked 1 as a cyclosporin A plus corticosteroid resistance gene","volume":"112","author":"Chang","year":"2020","journal-title":"J Autoimmun."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e28085","article-title":"Identification of Y\u2212linked biomarkers and exploration of immune infiltration of normal-appearing gray matter in multiple sclerosis by bioinformatic analysis","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012167","article-title":"Role of endothelial STAT3 in cerebrovascular function and protection from ischemic brain injury","volume":"23","author":"Davis","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201474","article-title":"Analysis of four neuroligin genes as candidates for autism","volume":"13","author":"Ylisaukko-oja","year":"2005","journal-title":"Eur J Hum Genet"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705895114","article-title":"Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y","volume":"115","author":"Bogaert","year":"2018","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.2015.14.issue-2","article-title":"Behavioral phenotypes in males with XYY and possible role of increased NLGN4Y expression in autism features","volume":"14","author":"Ross","year":"2015","journal-title":"Genes Brain Behav"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.02.016","article-title":"Sex differences in pediatric traumatic brain injury","volume":"317","author":"Arambula","year":"2019","journal-title":"Exp Neurol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7508\/ibj.2016.02.007","article-title":"Investigation of histone lysine-specific demethylase 5D KDM5D) isoform expression in prostate cancer cell lines: a system approach","volume":"20","author":"Jangravi","year":"2016","journal-title":"Iran BioMed J"},{"key":"B44","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nrm3327","article-title":"Molecular mechanisms and potential functions of histone demethylases","volume":"13","author":"Kooistra","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0230-6","article-title":"The cancer driver genes IDH1\/2, JARID1C\/KDM5C, and UTX\/KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism","volume":"51","author":"Chang","year":"2019","journal-title":"Exp Mol Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvy106","article-title":"KDM5D-mediated H3K4 demethylation is required for sexually dimorphic gene expression in mouse embryonic fibroblasts","volume":"165","author":"Mizukami","year":"2019","journal-title":"J Biochem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123048","article-title":"Proteasome and autophagy-mediated impairment of late long-term potentiation (l-LTP) after traumatic brain injury in the somatosensory cortex of mice","volume":"20","author":"Feldmann","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.brainres.2014.03.017","article-title":"Identification of sexually dimorphic genes in the neonatal mouse cortex and hippocampus","volume":"1562","author":"Armoskus","year":"2014","journal-title":"Brain Res"},{"key":"B49","volume-title":"Regulation of Neuronal Development and Function by the Intellectual Disability-Associated Transcriptional Regulator KDM5","author":"Hatch","year":"2022"},{"key":"B50","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ijdevneu.2019.07.011","article-title":"Androgenic regulation of sexually dimorphic expression of RNA binding motif protein 48 in the developing mouse cortex and hippocampus","volume":"78","author":"Franklin","year":"2019","journal-title":"Int J Dev Neurosci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s00109-014-1122-9","article-title":"Linking STAT and TLR signaling in microglia: a new role for the histone demethylase Jmjd3","volume":"92","author":"Hanisch","year":"2014","journal-title":"J Mol Med (Berl)"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.144","article-title":"Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury","volume":"33","author":"Zhao","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/str.50.suppl_1.23","article-title":"Abstract 23: circulating peripheral factors induce age-related epigenetic changes in microglia which induces a primed phenotype","volume":"50","author":"Koellhoffer","year":"2019","journal-title":"Stroke"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171417","article-title":"Macrophage\/microglial Ezh2 facilitates autoimmune inflammation through inhibition of Socs3","volume":"215","author":"Zhang","year":"2018","journal-title":"J Exp Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.05.020","article-title":"White matter damage after traumatic brain injury: A role for damage associated molecular patterns","volume":"1863","author":"Braun","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.bbi.2015.06.020","article-title":"Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor","volume":"50","author":"Xu","year":"2015","journal-title":"Brain Behav Immun"},{"key":"B57","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s12974-016-0738-9","article-title":"Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation","volume":"13","author":"Corrigan","year":"2016","journal-title":"J Neuroinflamm"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0358-z","article-title":"CD40 negatively regulates ATP-TLR4-activated inflammasome in microglia","volume":"37","author":"Gaikwad","year":"2017","journal-title":"Cell Mol Neurobiol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.03.004","article-title":"The emerging role of neutrophils as modifiers of recovery after traumatic injury to the developing brain","volume":"317","author":"von Leden","year":"2019","journal-title":"Exp Neurol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12974-018-1173-x","article-title":"Neutrophils in traumatic brain injury (TBI): friend or foe","volume":"15","author":"Liu","year":"2018","journal-title":"J Neuroinflamm"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23764","article-title":"The clinical significance of spondin 2 eccentric expression in peripheral blood mononuclear cells in bronchial asthma","volume":"35","author":"Zhou","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"B62","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ebiom.2019.02.040","article-title":"Proteomics based identification of KDM5 histone demethylases associated with cardiovascular disease","volume":"41","author":"Mokou","year":"2019","journal-title":"EBioMedicine"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.93","article-title":"Epigenetic mechanisms in cerebral ischemia","volume":"33","author":"Schweizer","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"B64","doi-asserted-by":"publisher","first-page":"110748","DOI":"10.1016\/j.brainresbull.2023.110748","article-title":"The X-linked histone demethylases KDM5C and KDM6A as regulators of T cell-driven autoimmunity in the central nervous system","volume":"202","author":"Fazazi","year":"2023","journal-title":"Brain Res Bull."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X21999553","article-title":"Transcriptome analysis reveals sexual disparities in gene expression in rat brain microvessels","volume":"41","author":"Chandra","year":"2021","journal-title":"J Cereb Blood Flow Metab"},{"key":"B66","doi-asserted-by":"publisher","first-page":"44876","DOI":"10.1038\/srep44876","article-title":"Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma","volume":"7","author":"Arseneault","year":"2017","journal-title":"Sci Rep"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06254-7","article-title":"Histone demethylase KDM5D upregulation drives sex differences in colon cancer","volume":"619","author":"Li","year":"2023","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3011383","article-title":"Epigenetic regulation by lysine demethylase 5 (KDM5) enzymes in cancer","volume":"3","author":"Blair","year":"2011","journal-title":"Cancers (Basel)"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13898","article-title":"Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI","volume":"20","author":"Shahim","year":"2024","journal-title":"Alzheimers Dement"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-020-01058-3","article-title":"Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study","volume":"27","author":"Li","year":"2020","journal-title":"Breast Cancer"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1538561\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T09:24:08Z","timestamp":1742808248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1538561\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":70,"alternative-id":["10.3389\/fimmu.2025.1538561"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1538561","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]},"article-number":"1538561"}}