{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:11:57Z","timestamp":1788930717842,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Mass Spectrom"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Membrane\u2010associated proteins, including those embedded in exosomal membranes or bound to plasma lipids, are promising disease biomarkers. However, their hydrophobic nature limits detection through conventional proteomic workflows, which primarily capture soluble proteins. In this study, we developed and optimized a lipase\u2010based pretreatment strategy to improve the detection of insoluble membrane proteins in human plasma. Lipase treatment using porcine pancreas\u2010derived enzymes was optimized to 37\u00b0C, 3\u2009U, and 1\u2009h, based on overall protein yield and membrane protein enrichment. Sequential application after depletion of high\u2010abundance proteins increased the proportion of membrane proteins from 12%\u201320%. Using this optimized workflow, we performed data\u2010independent acquisition\u2010based LC\u2013MS\/MS analysis of plasma samples from patients with early\u2010stage breast cancer and benign disease (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096 each). Notably, 38% of the uniquely detected or enriched proteins in cancer plasma were membrane\u2010associated. Among them, protocadherin 12 (PCDH12) was significantly elevated in the plasma of patients with breast cancer, indicating its potential as a novel diagnostic biomarker. This study highlights the use of lipase\u2010enhanced proteomics for revealing plasma membrane proteins and advancing noninvasive biomarker discovery for cancer.\n                  <\/jats:p>","DOI":"10.1002\/jms.70104","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:33:36Z","timestamp":1787034816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Breast Cancer Diagnostic Markers Using Lipase\u2010Based Plasma Proteomics of Lipid\u2010Bound Proteins"],"prefix":"10.1002","volume":"61","author":[{"given":"Eun Joo","family":"Kang","sequence":"first","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-4771","authenticated-orcid":false,"given":"Youngshik","family":"Choe","sequence":"additional","affiliation":[{"name":"Korea Brain Research Institute  Daegu Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-3333","authenticated-orcid":false,"given":"Kwan Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-701X","authenticated-orcid":false,"given":"Sangkyu","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1408415"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0706-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023090"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm529"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12855"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-025-02282-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-015-8732-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(65)90082-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R200012-JLR200"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83748-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12803"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4048\/jbc.2023.26.e27"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2024.252"},{"issue":"8","key":"e_1_2_8_15_1","first-page":"2357","article-title":"A re\u2010Evaluation of Carcinoembryonic Antigen (CEA) as a Serum Marker for Breast Cancer: A Prospective Longitudinal Study","volume":"7","author":"Guadagni F.","year":"2001","journal-title":"Clinical Cancer Research"},{"issue":"6","key":"e_1_2_8_16_1","first-page":"7549","article-title":"Elevation of Serum CEA and CA15\u20103 Levels During Antitumor Therapy Predicts Poor Therapeutic Response in Advanced Breast Cancer Patients","volume":"14","author":"Yang Y.","year":"2017","journal-title":"Oncology Letters"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-019-05357-y"},{"key":"e_1_2_8_18_1","article-title":"Prognostic Models for Nonmetastatic Triple\u2010Negative Breast Cancer Based on the Pretreatment Serum Tumor Markers With Machine Learning","volume":"2021","author":"Chen H.","year":"2021","journal-title":"Journal of Oncology"},{"issue":"4","key":"e_1_2_8_19_1","article-title":"The Influence of Tumor\u2010Specific Markers in Breast Cancer on Other Blood Parameters","volume":"14","author":"Varzaru V. B.","year":"2024","journal-title":"Life (Basel)"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.70127"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6c00078"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-17857-x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-021-06379-1"}],"container-title":["Journal of Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jms.70104","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jms.70104","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jms.70104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:05:52Z","timestamp":1788930352000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jms.70104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/jms.70104"],"URL":"https:\/\/doi.org\/10.1002\/jms.70104","archive":["Portico"],"relation":{},"ISSN":["1076-5174","1096-9888"],"issn-type":[{"value":"1076-5174","type":"print"},{"value":"1096-9888","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70104"}}