{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T19:26:00Z","timestamp":1786303560091,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":164,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170577"],"award-info":[{"award-number":["82170577"]}],"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":["81970479"],"award-info":[{"award-number":["81970479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Provincial Natural Science Foundation of Guangdong","award":["2023A1515010187"],"award-info":[{"award-number":["2023A1515010187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P\u2009&amp;lt;\u20090.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix\u2013receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/gastro\/goad031","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T02:20:38Z","timestamp":1686622838000},"source":"Crossref","is-referenced-by-count":11,"title":["The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study"],"prefix":"10.1093","volume":"11","author":[{"given":"Songfeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangbin","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Hou","sequence":"additional","affiliation":[{"name":"Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianjun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niandi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2838-1103","authenticated-orcid":false,"given":"Mengyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixian","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"2023061302200413800_goad031-B1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/nyas.13176","article-title":"Achalasia: from diagnosis to management","volume":"1381","author":"Vaezi","year":"2016","journal-title":"Ann N Y Acad Sci"},{"key":"2023061302200413800_goad031-B2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41572-022-00356-8","article-title":"Achalasia","volume":"8","author":"Savarino","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"2023061302200413800_goad031-B3","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.14309\/ajg.0000000000000731","article-title":"ACG clinical guidelines: diagnosis and management of achalasia","volume":"115","author":"Vaezi","year":"2020","journal-title":"Am J 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of 2\u2005years","volume":"65","author":"Werner","year":"2016","journal-title":"Gut"},{"key":"2023061302200413800_goad031-B10","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.cgh.2021.02.035","article-title":"Epidemiologic and economic burden of achalasia in the United States","volume":"20","author":"Gaber","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2023061302200413800_goad031-B11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/1751-2980.12973","article-title":"The etiology of achalasia: an immune-dominant disease","volume":"22","author":"Wu","year":"2021","journal-title":"J Dig Dis"},{"key":"2023061302200413800_goad031-B12","doi-asserted-by":"crossref","first-page":"e00388","DOI":"10.14309\/ctg.0000000000000388","article-title":"The number of interstitial cells of Cajal differs among different subtypes of achalasia and is related to patients' prognosis","volume":"12","author":"Chen","year":"2021","journal-title":"Clin Transl 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