{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:13:06Z","timestamp":1784146386232,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sichuan Science and Technology Program","award":["23ZDYF2116"],"award-info":[{"award-number":["23ZDYF2116"]}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["ZYGD18022"],"award-info":[{"award-number":["ZYGD18022"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["2020HXBH028"],"award-info":[{"award-number":["2020HXBH028"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["2021HXFH008"],"award-info":[{"award-number":["2021HXFH008"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2021YFS0198"],"award-info":[{"award-number":["2021YFS0198"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009579","name":"Health Department of Sichuan Province","doi-asserted-by":"publisher","award":["20PJ047"],"award-info":[{"award-number":["20PJ047"]}],"id":[{"id":"10.13039\/501100009579","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Sichuan Science and Technology Program","award":["2023YFSY0039"],"award-info":[{"award-number":["2023YFSY0039"]}]},{"DOI":"10.13039\/501100019014","name":"Chengdu Science and Technology Program","doi-asserted-by":"publisher","award":["2022-YF05-01497"],"award-info":[{"award-number":["2022-YF05-01497"]}],"id":[{"id":"10.13039\/501100019014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Primary aldosteronism (PA), a significant cause of secondary hypertension affecting \u223c10% of patients with severe hypertension, exacerbates cardiovascular, and cerebrovascular complications even after blood pressure control. PA is categorized into two main subtypes: unilateral aldosterone-producing adenomas (APA) and bilateral hyperaldosteronism (BHA), each requiring distinct treatment approaches. Accurate subtype classification is crucial for selecting the most effective treatment. The goal of this study was to develop novel blood-based proteomic biomarkers to differentiate between APA and BHA subtypes in patients with PA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Methods<\/jats:title>\n                  <jats:p>Five subtyping differential protein biomarker candidates (APOC3, CD56, CHGA, KRT5, and AZGP1) were identified through targeted proteomic profiling of plasma. The subtyping efficiency of these biomarkers was assessed at both the tissue gene expression and blood protein expression levels. To explore the underlying biology of APA and BHA, significant differential pathways were investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The five-protein panel proved highly effective in distinguishing APA from BHA in both tissue and blood samples. By integrating these five protein biomarkers with aldosterone and renin, our blood-based predictive methods achieved remarkable receiver operating characteristic (ROC) area under the ROC curves of 0.986 (95% CI: 0.963-1.000) for differentiating essential hypertension from PA, and 0.922 (95% CI: 0.846-0.998) for subtyping APA versus BHA. These outcomes surpass the performance of the existing Kobayashi score subtyping system. Furthermore, the study validated differential pathways associated with the pathophysiology of PA, aligning with current scientific knowledge and opening new avenues for advancing PA care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The new blood-based biomarkers for PA subtyping hold the potential to significantly enhance clinical utility and advance the practice of PA care.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae148","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T17:27:47Z","timestamp":1731950867000},"page":"558-569","source":"Crossref","is-referenced-by-count":8,"title":["Targeted multiplex proteomics for the development and validation of biomarkers in primary aldosteronism subtyping"],"prefix":"10.1093","volume":"191","author":[{"given":"Fangli","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Endocrinology, West China Hospital, Sichuan University , Chengdu 610041, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Ding","sequence":"additional","affiliation":[{"name":"mProbe Inc. 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Research and Development Department, , Rockville, MD 20850 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jin","sequence":"additional","affiliation":[{"name":"mProbe Inc. Research and Development Department, , Rockville, MD 20850 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C James","family":"Chou","sequence":"additional","affiliation":[{"name":"mProbe Inc. Research and Development Department, , Rockville, MD 20850 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Schilling","sequence":"additional","affiliation":[{"name":"mProbe Inc. Research and Development Department, , Rockville, MD 20850 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben Y","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, West China Hospital, Sichuan University , Chengdu 610041, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl G","family":"Sylvester","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Whitin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey J","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doff B","family":"McElhinney","sequence":"additional","affiliation":[{"name":"Departments of Cardiothoracic Surgery and Pediatrics (Cardiology), Stanford University School of Medicine , Stanford, CA 94305 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, West China Hospital, Sichuan University , Chengdu 610041, Sichuan 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