{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T21:52:49Z","timestamp":1780782769148,"version":"3.54.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"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":"\n Background<\/jats:title>\n Acute myeloid leukemia (AML) is a hematological malignancy with a high incidence of febrile neutropenia during the first two treatment cycles. This study aims to develop a gene signature related to neutrophil extracellular traps (NETs) to enhance understanding of AML mechanisms and identify potential prognostic biomarkers.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A consistent cluster analysis was conducted on 151 AML patients from the TCGA dataset. A differential analysis was performed to identify the differentially expressed genes (DEGs) specific to different subtypes and the training cohort (normal vs tumour). The NETs-related differentially expressed genes (NR-DEGs) were obtained through the overlapping of the two sets of differentially expressed genes. Univariate Cox and Least absolute shrinkage and selection operator (LASSO) regression analysis were employed to construct a NETs-related AML prognostic signature. Furthermore, an immune feature estimation and functional enrichment analysis was conducted between the two risk subgroups.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Two distinct AML subtypes were identified, exhibiting markedly disparate survival outcomes. A total of 1,700 and 1,941 DEGs were identified in the different subtypes and training cohort (normal vs. tumour), respectively. Thirteen NR-DEGs were identified. Subsequently, a NETs-related prognostic signature was constructed based on the 3 prognostic genes (\n MPO<\/jats:italic>\n ,\n CCL3<\/jats:italic>\n , and\n TLR8<\/jats:italic>\n ). An independent prognostic analysis indicated that the risk score and age could be employed as independent prognostic factors. Our findings revealed the presence of five markedly differentially expressed immune cells between the two risk subgroups. Ultimately, it was determined that all three genes were associated with the \u2018chemokine signalling pathway\u2019.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The prognostic signature comprised of\n MPO<\/jats:italic>\n ,\n CCL3<\/jats:italic>\n , and\n TLR8<\/jats:italic>\n based on NETs was established, which provided theoretical basis and reference value for the research of AML.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1580750","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:27:00Z","timestamp":1761283620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Establishment of prognostic signature based on neutrophil extracellular traps-related genes in acute myeloid leukemia: a bioinformatics analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhenglei","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunmei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghua","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasar Mehmood","family":"Yousafzai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zia","family":"Asad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyu","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.2928","article-title":"Therapeutic advances in acute myeloid leukemia","volume":"29","author":"Burnett","year":"2011","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"106936","DOI":"10.1016\/j.ijsu.2022.106936","article-title":"Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery","volume":"72","author":"Zou","year":"2022","journal-title":"Int J Surg"},{"key":"B3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s41375-020-01069-1","article-title":"New strategies to treat AML: novel insights into AML survival pathways and combination therapies","volume":"35","author":"Nair","year":"2021","journal-title":"Leukemia."},{"key":"B4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41586-024-08107-3","article-title":"Origins and impact of extrachromosomal DNA","volume":"613","author":"Bailey","year":"2023","journal-title":"Nature."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0222-4","article-title":"Tumour-associated neutrophils in patients with cancer","volume":"16","author":"Shaul","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1186\/1471-2105-8-423","article-title":"PubMed related articles: a probabilistic topic-based model for content similarity","volume":"8","author":"Lin","year":"2007","journal-title":"BMC Bioinf"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1047367","article-title":"Identification of renal ischemia reperfusion injury subtypes","volume":"13","author":"Wu","year":"2022","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"7948","DOI":"10.1038\/s41598-022-12087-7","article-title":"A fusion approach to improve accuracy and estimate prediction interval for cuffless blood pressure monitoring","volume":"12","author":"Landry","year":"2022","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B11","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":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.900810","article-title":"Dominant myocardial fibrosis and complex immune microenvironment jointly shape the pathogenesis of arrhythmogenic right ventricular cardiomyopathy","volume":"9","author":"Lu","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.731048","article-title":"Hypoxia-related lncRNA correlates with prognosis and immune microenvironment in lower-grade glioma","volume":"12","author":"Xu","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1207642","article-title":"Molecular subtyping of acute myeloid leukemia through ferroptosis-derived signature","volume":"11","author":"Fu","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.8","article-title":"Expression of myeloperoxidase enhances the chemosensitivity of leukemia cells through the generation of reactive oxygen species and the nitration of protein","volume":"22","author":"Yamazaki","year":"2008","journal-title":"Leukemia."},{"key":"B16","doi-asserted-by":"publisher","first-page":"117071","DOI":"10.1016\/j.lfs.2019.117071","article-title":"Differential regulatory effects of chemotherapeutic protocol on CCL3, CCL4, CCL5, CCR5 axes in acute myeloid leukemia patients with monocytic lineage","volume":"240","author":"Yazdani","year":"2020","journal-title":"Life Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00006IF","article-title":"Anabolic effects of IGF-1 signaling on the skeleton","volume":"4","author":"Tahimic","year":"2013","journal-title":"Front Endocrinol"},{"key":"B18","first-page":"375","article-title":"Chemoreception","volume-title":"The physiology of fishes","author":"Sorenson","year":"1998"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.449926","article-title":"CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak","volume":"288","author":"Kremer","year":"2013","journal-title":"J Biol Chem"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2018.03.024","article-title":"CXCR4-mediated signaling regulates autophagy and influences acute myeloid leukemia cell survival and drug resistance","volume":"425","author":"Hu","year":"2018","journal-title":"Cancer Lett"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4843","article-title":"The interleukin-8 pathway in cancer","volume":"14","author":"Waugh","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.81","article-title":"Leukemia cell infiltration causes defective erythropoiesis partially through MIP-1\u03b1\/CCL3","volume":"30","author":"Wang","year":"2016","journal-title":"Leukemia."},{"key":"B23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s12288-014-0408-y","article-title":"Lack of correlation between the CCR5-\u039432 mutation and acute myeloid leukemia in Iranian patients","volume":"31","author":"Khorramdelazad","year":"2015","journal-title":"Indian J Hematol Blood Transfus."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP1TA3FLOQTMHF","article-title":"C-C chemokine receptor 1 expression in human hematolymphoid neoplasia","volume":"133","author":"Anderson","year":"2010","journal-title":"Am J Clin Pathol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00262-010-0917-y","article-title":"Targeting Toll-like receptor 7\/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation","volume":"60","author":"van den Ancker","year":"2011","journal-title":"Cancer Immunol Immunother."},{"key":"B26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s00262-009-0721-8","article-title":"The Toll-like receptor 7\/8 agonist resiquimod greatly increases the immunostimulatory capacity of human acute myeloid leukemia cells","volume":"59","author":"Smits","year":"2010","journal-title":"Cancer Immunol Immunother."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12416","article-title":"Tumor microenvironment signaling and therapeutics in cancer progression","volume":"43","author":"Goenka","year":"2023","journal-title":"Cancer Commun (Lond)."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.79438","article-title":"CXCL14 promotes metastasis of non-small cell lung cancer through ACKR2-depended signaling pathway","volume":"19","author":"Chang","year":"2023","journal-title":"Int J Biol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1580750\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:27:02Z","timestamp":1761283622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1580750\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2025.1580750"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1580750","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]},"article-number":"1580750"}}