{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:46:54Z","timestamp":1776329214499,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There is an urgent need for a companion assay to work with mesothelin-targeted therapeutic agents and for noninvasive and accurate prognostication of malignant mesothelioma (MM) patients. We report the development and validation of a blood-based assay for megakaryocyte potentiating factor (MPF) and the evaluation of its effectiveness for prognosis in MM and lung cancer patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using electrochemiluminescence technology, we developed a sensitive MPF assay and performed both analytical and clinical validations. Further, the effectiveness of the MPF assay in predicting prognosis was evaluated for 95 MM and 272 lung cancer patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We performed comprehensive analytical and clinical validation, including precision and accuracy, interference, preanalytical variables, sensitivity, and specificity for mesothelioma. In MM patients, increased serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (log-rank P = 0.003; n = 95). In refractory MM patients, increased MPF is a strong predictor of poor outcome with an HR = 6.12 (log-rank P = 0.0007; n = 57). In a lung cancer patient cohort, increased MPF is a predictor of poor survival, with an HR = 1.57 (log-rank P = 0.003; n = 272).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The MPF assay has robust technical characteristics, with strong analytic and clinical validation. Clinical studies indicate that increased serum MPF is a predictor of poor survival for MM patients, throughout the course of the disease. Increased MPF is also associated with poor overall survival for patients with newly diagnosed lung cancer.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/jalm.2017.025015","type":"journal-article","created":{"date-parts":[[2018,8,26]],"date-time":"2018-08-26T12:54:31Z","timestamp":1535288071000},"page":"166-177","source":"Crossref","is-referenced-by-count":10,"title":["Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer"],"prefix":"10.1093","volume":"3","author":[{"given":"Yunkai","family":"Yu","sequence":"first","affiliation":[{"name":"Genetics Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Br\u00edd M","family":"Ryan","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anish","family":"Thomas","sequence":"additional","affiliation":[{"name":"Thoracic and Gastrointestinal Oncology Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betsy","family":"Morrow","sequence":"additional","affiliation":[{"name":"Thoracic and Gastrointestinal Oncology Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Thoracic and Gastrointestinal Oncology Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Kang","sequence":"additional","affiliation":[{"name":"Genetics Branch"},{"name":"Basic Science Program, Leidos Biomedical Research, Inc., Frederick, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Zingone","sequence":"additional","affiliation":[{"name":"Laboratory of Human Carcinogenesis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Onda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffit","family":"Hassan","sequence":"additional","affiliation":[{"name":"Thoracic and Gastrointestinal Oncology Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ira","family":"Pastan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Cao","sequence":"additional","affiliation":[{"name":"Genetics Branch"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,9,1]]},"reference":[{"key":"2022020118360115500_B1","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1056\/NEJMra050152","article-title":"Adv in malignant mesothelioma","volume":"353","author":"Robinson","year":"2005","journal-title":"N Engl J Med"},{"key":"2022020118360115500_B2","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1200\/JCO.2003.11.136","article-title":"Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma","volume":"21","author":"Vogelzang","year":"2003","journal-title":"J Clin Oncol"},{"key":"2022020118360115500_B3","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1200\/JCO.2008.19.8523","article-title":"Malignant pleural mesothelioma","volume":"27","author":"Tsao","year":"2009","journal-title":"J Clin Oncol"},{"key":"2022020118360115500_B4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1073\/pnas.93.1.136","article-title":"Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers","volume":"93","author":"Chang","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022020118360115500_B5","doi-asserted-by":"crossref","first-page":"21984","DOI":"10.1074\/jbc.270.37.21984","article-title":"Molecular cloning and expression of megakaryocyte potentiating factor cDNA","volume":"270","author":"Kojima","year":"1995","journal-title":"J Biol Chem"},{"key":"2022020118360115500_B6","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/S0140-6736(03)14794-0","article-title":"Mesothelin-family proteins and diagnosis of mesothelioma","volume":"362","author":"Robinson","year":"2003","journal-title":"Lancet"},{"key":"2022020118360115500_B7","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/ijc.2910500308","article-title":"Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium","volume":"50","author":"Chang","year":"1992","journal-title":"Int J Cancer"},{"key":"2022020118360115500_B8","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0046-8177(03)00177-1","article-title":"Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas","volume":"34","author":"Frierson","year":"2003","journal-title":"Hum Pathol"},{"key":"2022020118360115500_B9","first-page":"181","article-title":"Characterization of the antigen (CAK1) recognized by monoclonal antibody k1 present on ovarian cancers and normal mesothelium","volume":"52","author":"Chang","year":"1992","journal-title":"Cancer Res"},{"key":"2022020118360115500_B10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/01.pai.00000141545.36485.d6","article-title":"Localization of mesothelin in epithelial ovarian cancer","volume":"13","author":"Hassan","year":"2005","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"2022020118360115500_B11","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1097\/00000478-200311000-00003","article-title":"Application of mesothelin immunostaining in tumor diagnosis","volume":"27","author":"Ordonez","year":"2003","journal-title":"Am J Surg Pathol"},{"key":"2022020118360115500_B12","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1158\/1078-0432.CCR-03-0801","article-title":"Mesothelin: a new target for immunotherapy","volume":"10","author":"Hassan","year":"2004","journal-title":"Clin Cancer Res"},{"key":"2022020118360115500_B13","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1158\/0008-5472.CAN-14-0337","article-title":"Discovery of mesothelin and exploiting it as a target for immunotherapy","volume":"74","author":"Pastan","year":"2014","journal-title":"Cancer Res"},{"key":"2022020118360115500_B14","doi-asserted-by":"crossref","first-page":"208ra147","DOI":"10.1126\/scitranslmed.3006941","article-title":"Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression","volume":"5","author":"Hassan","year":"2013","journal-title":"Sci Transl Med"},{"key":"2022020118360115500_B15","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/00000478-200308000-00001","article-title":"The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma","volume":"27","author":"Ordonez","year":"2003","journal-title":"Am J Surg Pathol"},{"key":"2022020118360115500_B16","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/00000478-200302000-00002","article-title":"Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura","volume":"27","author":"Miettinen","year":"2003","journal-title":"Am J Surg Pathol"},{"key":"2022020118360115500_B17","doi-asserted-by":"crossref","first-page":"11694","DOI":"10.18632\/oncotarget.3429","article-title":"High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis","volume":"6","author":"Thomas","year":"2015","journal-title":"Oncotarget"},{"key":"2022020118360115500_B18","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1158\/1078-0432.CCR-13-1862","article-title":"Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma","volume":"20","author":"Kachala","year":"2014","journal-title":"Clin Cancer Res"},{"key":"2022020118360115500_B19","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1373\/clinchem.2006.079327","article-title":"MESOMARK: a potential test for malignant pleural mesothelioma","volume":"53","author":"Beyer","year":"2007","journal-title":"Clin Chem"},{"key":"2022020118360115500_B20","unstructured":"Fujirebio\n              \u00a0Diagnostics\n          . Mesomark Patient Information. https:\/\/www.accessdata.fda.gov\/cdrh_docs\/pdf6\/H060004C.pdf (Accessed Novermber 2017)."},{"key":"2022020118360115500_B21","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/bjc.2017.22","article-title":"Prognostication and monitoring of mesothelioma using biomarkers: a systematic review","volume":"116","author":"Arnold","year":"2017","journal-title":"Br J Cancer"},{"key":"2022020118360115500_B22","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1136\/thoraxjnl-2014-205205","article-title":"Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma","volume":"69","author":"Creaney","year":"2014","journal-title":"Thorax"},{"key":"2022020118360115500_B23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.lungcan.2013.09.016","article-title":"Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma","volume":"82","author":"Creaney","year":"2013","journal-title":"Lung Cancer"},{"key":"2022020118360115500_B24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1158\/2159-8290.CD-15-0583","article-title":"Mesothelin-targeted cars: driving t cells to solid tumors","volume":"6","author":"Morello","year":"2016","journal-title":"Cancer Discov"},{"key":"2022020118360115500_B25","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1200\/JCO.2016.68.3672","article-title":"Mesothelin immunotherapy for cancer: ready for prime time?","volume":"34","author":"Hassan","year":"2016","journal-title":"J Clin Oncol"},{"key":"2022020118360115500_B26","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1158\/1078-0432.CCR-06-0472","article-title":"Megakaryocyte potentiation factor cleaved from mesothelin precursor is a useful tumor marker in the serum of patients with mesothelioma","volume":"12","author":"Onda","year":"2006","journal-title":"Clin Cancer Res"},{"key":"2022020118360115500_B27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.lungcan.2008.02.012","article-title":"Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin","volume":"62","author":"Iwahori","year":"2008","journal-title":"Lung Cancer"},{"key":"2022020118360115500_B28","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1164\/rccm.200907-1020OC","article-title":"Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma","volume":"181","author":"Hollevoet","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2022020118360115500_B29","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1158\/1078-0432.CCR-09-2167","article-title":"Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents","volume":"16","author":"Dancey","year":"2010","journal-title":"Clin Cancer Res"},{"key":"2022020118360115500_B30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s11095-005-9045-3","article-title":"Fit-for-purpose method development and validation for successful biomarker measurement","volume":"23","author":"Lee","year":"2006","journal-title":"Pharm Res"},{"key":"2022020118360115500_B31","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1002\/cncr.28875","article-title":"Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125","volume":"120","author":"Hassan","year":"2014","journal-title":"Cancer"},{"key":"2022020118360115500_B32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1158\/1055-9965.EPI-08-0705","article-title":"Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians","volume":"18","author":"Enewold","year":"2009","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2022020118360115500_B33","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/jnci\/djr216","article-title":"Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer","volume":"103","author":"Pine","year":"2011","journal-title":"J Natl Cancer Inst"},{"key":"2022020118360115500_B34","doi-asserted-by":"crossref","first-page":"e004145","DOI":"10.1136\/bmjopen-2013-004145","article-title":"Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis","volume":"4","author":"Cui","year":"2014","journal-title":"BMJ Open"},{"key":"2022020118360115500_B35","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s10549-014-3077-5","article-title":"Mesothelin expression is associated with poor outcomes in breast cancer","volume":"147","author":"Li","year":"2014","journal-title":"Breast Cancer Res Treat"},{"key":"2022020118360115500_B36","first-page":"449","article-title":"Biomarkers and prognostic factors for mesothelioma","volume":"1","author":"Pass","year":"2012","journal-title":"Ann Cardiothorac Surg"},{"key":"2022020118360115500_B37","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1056\/NEJMoa1115050","article-title":"Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma","volume":"367","author":"Pass","year":"2012","journal-title":"N Engl J Med"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/3\/2\/166\/42354399\/3_3_2_166.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/3\/2\/166\/42354399\/3_3_2_166.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T18:54:37Z","timestamp":1643741677000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/3\/2\/166\/5603053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,1]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,9,1]]},"published-print":{"date-parts":[[2018,9,1]]}},"URL":"https:\/\/doi.org\/10.1373\/jalm.2017.025015","relation":{},"ISSN":["2576-9456","2475-7241"],"issn-type":[{"value":"2576-9456","type":"print"},{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,9,1]]},"published":{"date-parts":[[2018,9,1]]}}}