{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:12Z","timestamp":1785387612404,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Malignant pleural effusion (MPE) is a common manifestation in advanced malignancies. However, its differentiation from benign pleural effusions, such as parapneumonic effusion (PPE) and tuberculous pleural effusion (TPE), remains challenging. This study aimed to profile differentially expressed proteins and metabolites between MPE, PPE, and TPE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Pleural effusion samples from patients with MPE, PPE, and TPE were collected and subjected to proteomic and metabolomic profiling. Differentially expressed proteins (DEPs) and differentially abundant metabolites (DAMs) were identified, followed by functional enrichment analyzes. Integrated proteome\u2013metabolome analysis was performed to construct protein\u2013metabolite interaction networks and reveal key pathways associated with malignant and benign pleural effusions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Proteomic and metabolomic profiles differed significantly between MPE and non\u2010MPE. Arginine\u2010proline and glutamate metabolism were commonly enriched at both protein and metabolite levels in MPE versus PPE and TPE. At the protein level, Isocitrate Dehydrogenase 1 (IDH1) was significantly upregulated in MPE compared with both PPE and TPE. At the metabolite level, sarcosine and\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamine were markedly elevated, while creatine was significantly decreased in MPE. Integrated analysis further indicated that these four molecules play important roles in distinguishing MPE from PPE and TPE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Combined proteomic and metabolomic analyzes revealed the critical involvement of IDH1 in glutamate metabolism and arginine and proline metabolic pathways during MPE metabolic reprogramming. Identified molecules, including IDH1,\n                      <jats:sc>l<\/jats:sc>\n                      \u2010glutamine, creatine, and sarcosine, may serve as potential diagnostic biomarkers for differentiating malignant from benign pleural effusions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70356","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:57:58Z","timestamp":1784264278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Analysis Reveals Differentially Expressed Proteins and Metabolites in Malignant Pleural Effusion"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7650-537X","authenticated-orcid":false,"given":"Senlin","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Key Laboratory Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-4201","authenticated-orcid":false,"given":"Zhicheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Key Laboratory Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Key Laboratory Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9366-5444","authenticated-orcid":false,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Key Laboratory Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-7183","authenticated-orcid":false,"given":"Tingwang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Key Laboratory Affiliated Changshu Hospital of Nantong University  Changshu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Textbook of Pleural Diseases","author":"Richard W. L.","year":"2016"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2025-0197"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2023.101800"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0590-4"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.02.052"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2023.07.4220"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thorsurg.2012.10.004"},{"key":"e_1_2_12_9_1","volume-title":"Management of Pleural Effusion and Haemothorax","author":"Davide C.","year":"2016"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2025.02.001"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2019.02.64"},{"key":"e_1_2_12_12_1","article-title":"Blind Pleural Biopsy in the Study of Undiagnosed Pleural Effusion: Results and Complications","volume":"56","author":"Cabral M. B.","year":"2020","journal-title":"European Respiratory Journal"},{"issue":"21","key":"e_1_2_12_13_1","first-page":"377","article-title":"Pleural Effusion in Adults\u2010Etiology, Diagnosis, and Treatment","volume":"116","author":"Jany B.","year":"2019","journal-title":"Deutsches \u00c4rzteblatt International"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000468545"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-012-6117-1"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-013-7061-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115701646310314240910082445"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32115"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15070428"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.119734"},{"key":"e_1_2_12_21_1","article-title":"Diagnostic and Therapeutic Application of Proteomics in Infectious Disease","volume":"2023","author":"Fanuel B. Y.","year":"2023","journal-title":"Advances in Cell and Gene Therapy"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2025.120258"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.09.025"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2021.1908588"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2022.2158779"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/OAEM.S29942"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115701808287654240126112003"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1318.044"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jccs.201400350"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115701646291510240212091951"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms\/132885"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2024.105201"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6758"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93032-y"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwaf011"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2024.70.4.38"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb44070206"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429290327240222061812"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201591041"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73245"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13070865"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.8.1249"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13050515"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2018.01.023"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19072054"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02092-2"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00776"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2024.2367129"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.02.005"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.114943"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-00971-9"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00909-0"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202415698"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70356","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.70356","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:35:32Z","timestamp":1785386132000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.70356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":52,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/1759-7714.70356"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.70356","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70356"}}