{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T09:35:46Z","timestamp":1768383346156,"version":"3.49.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disorder caused by excessive immune activation. This exploratory study aimed to systematically identify potential diagnostic key genes linked to iron metabolism during HLH progression using comprehensive bioinformatics analysis and explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty peripheral blood mononuclear cell (PBMC) samples\u201415 from patients with HLH and 15 controls\u2014were analyzed through mRNA sequencing. Total RNA was extracted from these samples. First, the overlap between differentially expressed genes (DEGs) and iron metabolism-related genes (FeRGs) was identified to select candidate genes. Key genes were then derived using the Boruta method and least absolute shrinkage and selection operator (LASSO) regression analysis. Further investigations, including correlation, functional, and enrichment analyses, as well as immune infiltration and drug prediction, were performed to explore the molecular mechanisms. Finally, reverse transcription quantitative PCR (RT-qPCR) was used to validate the expression levels of the key genes in clinical specimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The intersection of 464 DEGs and 520 FeRGs identified 10 candidate genes. Machine learning analysis identified ALOX15, CAT, HBZ, MT2A, and CYGB as HLH key genes. A significant positive correlation was observed between ALOX15 and HBZ, while ALOX15 showed a notable negative correlation with CYGB and MT2A (|correlation coefficient (r)|\u202f&amp;gt;\u202f0.3,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). These key genes were functionally associated with antioxidant activity, toxic substance response, and inorganic compound detoxification, primarily involved in oxidative phosphorylation and Huntington\u2019s disease-related pathways. Notably, ALOX15 and CAT were significantly correlated with activated dendritic cells and CD4 memory T cells. Drug prediction revealed 15 compounds targeting ALOX15, MT2A, and CAT. Expression of ALOX15, CAT, and HBZ was down-regulated, while MT2A and CYGB were up-regulated in the HLH group, consistent with differential expression trends.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified five validated key genes\u2014ALOX15, CAT, HBZ, MT2A, and CYGB\u2014offering new insights into HLH pathogenesis and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1685793","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:16:19Z","timestamp":1768367779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of iron metabolism-related key genes and exploration of their potential mechanisms in hemophagocytic lymphohistiocytosis based on transcriptome sequencing"],"prefix":"10.3389","volume":"12","author":[{"given":"Li","family":"Fen","sequence":"first","affiliation":[{"name":"Hematology Department of Yunnan First People\u2019s Hospital, Kunming University of Science and Technology Affiliated Hospital, Yunnan Province Clinical Research Center for Hematologic Disease, Hu Yu Expert Workstation, Yunnan Province Major Difficult Diseases Traditional Chinese and Western Medicine Clinical Collaboration Pilot Project - Leukemia, Yunnan Provincial Clinical Medical Center for Blood Diseases and Thrombosis Prevention and Treatment, Yunnan Provincial Atherosclerosis Traditional Chinese and Western Medicine Collaborative Collaboration Base","place":["Kunming, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duan Hua","family":"Nan","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Clinical Medical Center for Digestive Diseases\/Gastroenterology, The First People's Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Lin","family":"Na","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Clinical Medical Center for Digestive Diseases\/Gastroenterology, The First People's Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Jie","sequence":"additional","affiliation":[{"name":"Hematology Department of Yunnan First People\u2019s Hospital, Kunming University of Science and Technology Affiliated Hospital, Yunnan Province Clinical Research Center for Hematologic Disease, Hu Yu Expert Workstation, Yunnan Province Major Difficult Diseases Traditional Chinese and Western Medicine Clinical Collaboration Pilot Project - Leukemia, Yunnan Provincial Clinical Medical Center for Blood Diseases and Thrombosis Prevention and Treatment, Yunnan Provincial Atherosclerosis Traditional Chinese and Western Medicine Collaborative Collaboration Base","place":["Kunming, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu Xue","family":"Zhong","sequence":"additional","affiliation":[{"name":"Hematology Department of Yunnan First People\u2019s Hospital, Kunming University of Science and Technology Affiliated Hospital, Yunnan Province Clinical Research Center for Hematologic Disease, Hu Yu Expert Workstation, Yunnan Province Major Difficult Diseases Traditional Chinese and Western Medicine Clinical Collaboration Pilot Project - Leukemia, Yunnan Provincial Clinical Medical Center for Blood Diseases and Thrombosis Prevention and Treatment, Yunnan Provincial Atherosclerosis Traditional Chinese and Western Medicine Collaborative Collaboration Base","place":["Kunming, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s00062-021-00998-3","article-title":"Central nervous system hemophagocytic lymphohistiocytosis (cns-hlh) from leptomeningeal anaplastic large cell lymphoma: mild clinical neurologic syndrome with extensive multifocal white matter disease","volume":"31","author":"Lehrer","year":"2021","journal-title":"Clin Neuroradiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s10875-020-00789-4","article-title":"Thinking beyond hlh: clinical features of patients with concurrent presentation of hemophagocytic lymphohistiocytosis and thrombotic microangiopathy","volume":"40","author":"Gloude","year":"2020","journal-title":"J Clin 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