{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:39:38Z","timestamp":1773013178797,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":163,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30772824"],"award-info":[{"award-number":["30772824"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81574031"],"award-info":[{"award-number":["81574031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019054","name":"Changsha Science and Technology Project","doi-asserted-by":"publisher","award":["K1501014-31"],"award-info":[{"award-number":["K1501014-31"]}],"id":[{"id":"10.13039\/501100019054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019054","name":"Changsha Science and Technology Project","doi-asserted-by":"publisher","award":["KC1704005"],"award-info":[{"award-number":["KC1704005"]}],"id":[{"id":"10.13039\/501100019054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005891","name":"State Administration of Traditional Chinese Medicine of the People's Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014978","name":"Hunan University of Chinese Medicine","doi-asserted-by":"publisher","award":["2022YF01"],"award-info":[{"award-number":["2022YF01"]}],"id":[{"id":"10.13039\/501100014978","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Nonspecific orbital inflammation (NSOI) is a heterogeneous inflammatory disorder of the orbit with an unclear etiology. ATP2A3, a key regulator of calcium homeostasis in the endoplasmic reticulum (ER), may play a pivotal role in NSOI pathogenesis. Its potential as a diagnostic biomarker merits thorough investigation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Differentially expressed genes (DEGs) common to two GEO datasets (GSE58331 and GSE105149) were intersected with immune\u2010related genes from the ImmPort database, yielding 89 candidates. ATP2A3 was prioritized using machine learning (ML) approaches, including LASSO, support vector machine (SVM)\u2010RFE, and weighted gene coexpression network analysis (WGCNA). Functional enrichment was assessed using GSEA and GSVA based on genes co\u2010expressed with ATP2A3. Immune microenvironment characteristics were evaluated using CIBERSORT and ESTIMATE. Expression of ATP2A3 was validated in GSE105149.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Fifteen hub genes were identified, with ATP2A3 strongly linked to immune\u2010related pathways. Genes positively correlated with ATP2A3 were enriched in sensory perception and extracellular matrix (ECM) organization. Immune infiltration analysis revealed a positive association between ATP2A3 expression and memory B cells, M2 macrophages, resting mast cells, monocytes, and regulatory T cells (Tregs), while naive B cells and plasma cells were negatively associated. ATP2A3 exhibited significant diagnostic potential for distinguishing NSOI.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    In the context of NSOI, we identify ATP2A3 as a novel contributor to immune\u2010driven pathogenesis. Its significant dysregulation in NSOI tissues relative to healthy controls underscores its potential as a prognostic marker within the inflammatory microenvironment.\n                  <\/jats:p>","DOI":"10.1155\/mi\/7061507","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:34:03Z","timestamp":1749807243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Regulation and ECM\u2010Related Pathway Enrichment Reveal ATP2A3 as a Prognostic Biomarker for Nonspecific Orbital Inflammation: An Integrated Machine Learning and Mendelian Randomization Analysis"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-9949","authenticated-orcid":false,"given":"Zixuan","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-9698","authenticated-orcid":false,"given":"Xiaolei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-1330","authenticated-orcid":false,"given":"Qinghua","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-021-02008-z"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/01676830.2017.1337185"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1722636"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-017-0610-7"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joco.2019.03.004"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2018.04.001"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.3458"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-023-09946-6"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031553"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2008.10.007"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22529"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5590-8"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22402"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22978"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2019.05.014"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22625"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-74409-1"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1318316"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcmed.2022.03.005"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158609"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcmed.2022.06.006"},{"key":"e_1_2_15_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-33277-x"},{"key":"e_1_2_15_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac498"},{"key":"e_1_2_15_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.054182"},{"key":"e_1_2_15_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051387"},{"key":"e_1_2_15_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.04.007"},{"key":"e_1_2_15_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110208"},{"key":"e_1_2_15_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-023-02822-5"},{"key":"e_1_2_15_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155103"},{"key":"e_1_2_15_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27064"},{"key":"e_1_2_15_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2019.1581227"},{"key":"e_1_2_15_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0000000000001161"},{"key":"e_1_2_15_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0000000000001022"},{"key":"e_1_2_15_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.982130"},{"key":"e_1_2_15_35_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.9802"},{"key":"e_1_2_15_36_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7588084"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-022-00412-0"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.858972"},{"key":"e_1_2_15_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0112s38"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/7061507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/mi\/7061507","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/7061507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:22:00Z","timestamp":1773008520000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/mi\/7061507"}},"subtitle":[],"editor":[{"given":"Palash","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/mi\/7061507"],"URL":"https:\/\/doi.org\/10.1155\/mi\/7061507","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"7061507"}}