{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:28:30Z","timestamp":1788532110671,"version":"build-2803163510"},"reference-count":24,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100017549","name":"Science and Technology Innovation 2025 Major Project of Ningbo Municipality","doi-asserted-by":"publisher","award":["2022Z134"],"award-info":[{"award-number":["2022Z134"]}],"id":[{"id":"10.13039\/501100017549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Moyamoya disease, a rare chronic cerebrovascular disorder, requires invasive digital subtraction angiography (DSA) for diagnosis. This study employed high-throughput proteomics to identify plasma biomarkers for Moyamoya disease diagnosis. We conducted immunopanel analysis using the Olink platform to evaluate 92 immune-related proteins in plasma samples from 88 Moyamoya disease patients and 88 healthy controls. Key proteins were identified through differential expression analysis, GO, and KEGG enrichment analysis. A diagnostic model was constructed using LASSO regression, Boruta algorithm, and machine learning models including random forest and XGBoost. Validation of these proteins was performed using GEO external data sets, followed by prediction of potential therapeutic drugs and molecular docking validation through pharmacogenomic databases. A total of 44 differentially expressed proteins were identified through the Olink immunopanel, with 12 downregulated and 32 upregulated. GO and KEGG analyses revealed significant enrichment of these proteins in innate immune responses and signaling pathways such as NF-kB and MAPK. Through LASSO, random forest, and protein under-area analysis, four potential biomarkers for Moyamoya disease (MGMT, SIT1, PRDX1, TRAF2) were identified. A diagnostic model using these proteins showed the highest AUC value with the XGBoost model. Additionally, TRAF2 and PRDX1 exhibited significant expression differences in Moyamoya disease patients within the GEO data set. Our study revealed the immune landscape of Moyamoya disease, identified four biomarkers, and established a variety of diagnostic models.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00310","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:53Z","timestamp":1785849053000},"page":"4823-4830","source":"Crossref","is-referenced-by-count":0,"title":["Identification\nof Immune Response-Related Proteomic\nBiomarkers in Moyamoya Disease Using Serum Olink Proteomics"],"prefix":"10.1021","volume":"25","author":[{"given":"Zhimeng","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Hou","sequence":"additional","affiliation":[{"name":"North China University of Science and Technology , , , ,","place":["Tangshan, Hebei, China, 063000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojin","family":"Ni","sequence":"additional","affiliation":[{"name":"Ningbo Hangzhou Bay Hospital , ,","place":["Ningbo, China, 315336"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wei","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-3212","authenticated-orcid":true,"given":"Liyuan","family":"Han","sequence":"additional","affiliation":[{"name":"Ningbo No. 2 Hospital , , , ,","place":["Ningbo, Zhejiang, China, 315000"]},{"name":"University of Chinese Academy of Sciences , , , ,","place":["Ningbo, Zhejiang, China, 315000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifeng","family":"Dai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youchao","family":"Xiao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8309-5372","authenticated-orcid":true,"given":"Jinghui","family":"Lin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Ningbo University , , , ,","place":["Ningbo, Zhejiang, China, 315010"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"1","key":"2026090409142081400_cit1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.5853\/jos.2015.01627","article-title":"Moyamoya\nDisease: Epidemiology, Clinical Features, and Diagnosis","volume":"18","author":"Kim","year":"2016","journal-title":"J. Stroke"},{"issue":"1","key":"2026090409142081400_cit2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1161\/STROKEAHA.107.490714","article-title":"Prevalence\nand clinicoepidemiological features of moyamoya disease in Japan:\nfindings from a nationwide epidemiological survey","volume":"39","author":"Kuriyama","year":"2008","journal-title":"Stroke"},{"issue":"8","key":"2026090409142081400_cit3","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1161\/STROKEAHA.119.024689","article-title":"Characteristics\nof Moyamoya Disease Based on National Registry Data in Japan","volume":"50","author":"Sato","year":"2019","journal-title":"Stroke"},{"issue":"7","key":"2026090409142081400_cit4","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.clineuro.2012.09.020","article-title":"An epidemiological\nsurvey of moyamoya disease, unilateral moyamoya disease and quasi-moyamoya\ndisease in Japan","volume":"115","author":"Hayashi","year":"2013","journal-title":"Clin. Neurol. Neurosurg."},{"issue":"6","key":"2026090409142081400_cit5","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3340\/jkns.2015.57.6.390","article-title":"Epidemiology\nof Moyamoya Disease in Korea: Based on National Health Insurance Service\nData","volume":"57","author":"Kim","year":"2015","journal-title":"J. Korean Neurosurg. Soc."},{"issue":"4","key":"2026090409142081400_cit6","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1136\/svn-2021-000909","article-title":"Incidence\nand prevalence of moyamoya disease in urban China: a nationwide retrospective\ncohort study","volume":"6","author":"Sun","year":"2021","journal-title":"Stroke Vasc. Neurol."},{"issue":"12","key":"2026090409142081400_cit7","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1161\/01.STR.24.12.1960","article-title":"Smooth muscle\ncell proliferation\nand localization of macrophages and T cells in the occlusive intracranial\nmajor arteries in moyamoya disease","volume":"24","author":"Masuda","year":"1993","journal-title":"Stroke"},{"issue":"2","key":"2026090409142081400_cit8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.5853\/jos.2014.16.2.65","article-title":"Genetics and\nBiomarkers of Moyamoya\nDisease: Significance of RNF213 as a Susceptibility Gene","volume":"16","author":"Fujimura","year":"2014","journal-title":"J. Stroke"},{"issue":"1","key":"2026090409142081400_cit9","doi-asserted-by":"publisher","first-page":"12","DOI":"10.5853\/jos.2015.01760","article-title":"The Pathophysiology of Moyamoya Disease:\nAn Update","volume":"18","author":"Bang","year":"2016","journal-title":"J. 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Belg."},{"issue":"1","key":"2026090409142081400_cit12","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1021\/acs.jproteome.0c00641","article-title":"Multiplatform Approach\nfor Plasma\nProteomics: Complementarity of Olink Proximity Extension Assay Technology\nto Mass Spectrometry-Based Protein Profiling","volume":"20","author":"Petrera","year":"2021","journal-title":"J. Proteome Res."},{"issue":"11","key":"2026090409142081400_cit13","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/S1474-4422(08)70240-0","article-title":"Moyamoya disease: current concepts\nand future perspectives","volume":"7","author":"Kuroda","year":"2008","journal-title":"Lancet Neurol."},{"issue":"5","key":"2026090409142081400_cit14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2176\/nmc.52.245","article-title":"Guidelines for diagnosis and treatment of moyamoya\ndisease (spontaneous occlusion of the circle of Willis)","volume":"52","author":"Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis; Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases.","year":"2012","journal-title":"Neurol. 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Biomed."},{"key":"2026090409142081400_cit23","doi-asserted-by":"publisher","first-page":"102347","DOI":"10.1016\/j.redox.2022.102347","article-title":"The antioxidant\nenzyme Peroxiredoxin-1 controls stroke-associated microglia against\nacute ischemic stroke","volume":"54","author":"Kim","year":"2022","journal-title":"Redox Biol."},{"key":"2026090409142081400_cit24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3389\/fnins.2020.00181","article-title":"Prdx1 Reduces Intracerebral\nHemorrhage-Induced\nBrain Injury via Targeting Inflammation- and Apoptosis-Related mRNA\nStability","volume":"14","author":"Yang","year":"2020","journal-title":"Front. Neurosci."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00310","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4823\/66294238\/acs.jproteome.6c00310.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4823\/66294238\/acs.jproteome.6c00310.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:06:10Z","timestamp":1788530770000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/9\/4823\/5234753\/Identification-of-Immune-Response-Related"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":24,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,9,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00310","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}