{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:53:42Z","timestamp":1775620422678,"version":"3.50.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0128836","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T00:51:32Z","timestamp":1433206292000},"page":"e0128836","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer"],"prefix":"10.1371","volume":"10","author":[{"given":"Pierre-Jean","family":"Lamy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Plassot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Louis","family":"Pujol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1016\/S0959-8049(97)00325-0","article-title":"Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party","volume":"33","author":"M Paesmans","year":"1997","journal-title":"Eur J Cancer"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0169-5002(97)00655-7","article-title":"Prognostic value of histology in patients with non-small cell lung cancer","volume":"17","author":"A Charloux","year":"1997","journal-title":"Lung Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1378\/chest.116.3.697","article-title":"Conditional survival among patients with carcinoma of the lung","volume":"116","author":"RM Merrill","year":"1999","journal-title":"Chest"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0169-5002(93)90179-2","article-title":"Analysis of early and late deaths on RTOG non-small cell carcinoma of the lung trials: comparison with CALGB 8433","volume":"10","author":"R Komaki","year":"1993","journal-title":"Lung Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1200\/JCO.1999.17.9.2692","article-title":"Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer","volume":"17","author":"K Furuse","year":"1999","journal-title":"J Clin Oncol"},{"key":"ref6","first-page":"247","article-title":"Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer","volume":"20","author":"A Depierre","year":"2002","journal-title":"J Clin Oncol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1378\/chest.111.6.1710","article-title":"Revisions in the International System for Staging Lung Cancer","volume":"111","author":"CF Mountain","year":"1997","journal-title":"Chest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0022-5223(19)39389-4","article-title":"Survival of patients surgically treated for stage I lung cancer","volume":"82","author":"DE Williams","year":"1981","journal-title":"J Thorac Cardiovasc Surg"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1042\/bj20020869","article-title":"A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein","volume":"368","author":"A Clauss","year":"2002","journal-title":"Biochem J"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1470-2045(06)70579-4","article-title":"Proteins with whey-acidic-protein motifs and cancer","volume":"7","author":"D Bouchard","year":"2006","journal-title":"Lancet Oncol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1093-3263(99)00023-6","article-title":"The whey acidic protein family: a new signature motif and three-dimensional structure by comparative modeling","volume":"17","author":"S Ranganathan","year":"1999","journal-title":"J Mol Graph Model"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1095\/biolreprod45.2.350","article-title":"A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors","volume":"45","author":"C Kirchhoff","year":"1991","journal-title":"Biol Reprod"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1465-9921-7-61","article-title":"WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung","volume":"7","author":"L Bingle","year":"2006","journal-title":"Respir Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1158\/0008-5472.CAN-04-3924","article-title":"Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas","volume":"65","author":"R Drapkin","year":"2005","journal-title":"Cancer Res"},{"key":"ref15","first-page":"3695","article-title":"The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma","volume":"63","author":"I Hellstrom","year":"2003","journal-title":"Cancer Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1158\/1078-0432.CCR-03-0409","article-title":"Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis","volume":"10","author":"KH Lu","year":"2004","journal-title":"Clin Cancer Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0378-1119(99)00342-X","article-title":"Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas","volume":"238","author":"M Schummer","year":"1999","journal-title":"Gene"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s13277-009-0015-y","article-title":"HE4: a new potential early biomarker for the recurrence of ovarian cancer","volume":"31","author":"E Anastasi","year":"2010","journal-title":"Tumour Biol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ygyno.2007.10.017","article-title":"The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass","volume":"108","author":"RG Moore","year":"2008","journal-title":"Gynecol Oncol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ygyno.2008.08.031","article-title":"A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass","volume":"112","author":"RG Moore","year":"2009","journal-title":"Gynecol Oncol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ygyno.2013.07.094","article-title":"Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer","volume":"131","author":"B Kristjansdottir","year":"2013","journal-title":"Gynecol Oncol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s13277-011-0256-4","article-title":"Human epididymis protein 4 reference limits and natural variation in a Nordic reference population","volume":"33","author":"N Bolstad","year":"2012","journal-title":"Tumour Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/sj.bjc.6605011","article-title":"Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts","volume":"100","author":"K Huhtinen","year":"2009","journal-title":"Br J Cancer"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/modpathol.3800612","article-title":"Comprehensive analysis of HE4 expression in normal and malignant human tissues","volume":"19","author":"MT Galgano","year":"2006","journal-title":"Mod Pathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s13277-010-0118-5","article-title":"Prognostic significance of HE4 expression in pulmonary adenocarcinoma","volume":"32","author":"S Yamashita","year":"2011","journal-title":"Tumour Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s13277-012-0427-y","article-title":"Evaluation of pleural fluid human epididymis 4 (HE4) as a marker of malignant pleural effusion","volume":"33","author":"MY Elsammak","year":"2012","journal-title":"Tumour Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1373\/clinchem.2010.157073","article-title":"Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases","volume":"57","author":"JM Escudero","year":"2011","journal-title":"Clin Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s13277-012-0356-9","article-title":"Serum HE4 as a diagnostic and prognostic marker for lung cancer","volume":"33","author":"K Iwahori","year":"2012","journal-title":"Tumour Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1007\/s13277-012-0499-8","article-title":"Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression","volume":"33","author":"S Yamashita","year":"2012","journal-title":"Tumour Biol"},{"key":"ref30","first-page":"5568","article-title":"Expression level of serum human epididymis 4 and its prognostic significance in human non-small cell lung cancer","volume":"7","author":"Y Jiang","year":"2014","journal-title":"Int J Clin Exp Med"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1200\/JCO.2012.42.6858","article-title":"Publication of tumor marker research results: the necessity for complete and transparent reporting","volume":"30","author":"LM McShane","year":"2012","journal-title":"J Clin Oncol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/ajcp\/77.2.123","article-title":"The World Health Organization histological typing of lung tumours","volume":"77","year":"1982","journal-title":"Am J Clin Pathol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1002\/1097-0142(19880601)61:11<2310::AID-CNCR2820611127>3.0.CO;2-X","article-title":"TNM classification of malignant tumors. A comparison between the new (1987) and the old editions","volume":"61","author":"LH Sobin","year":"1988","journal-title":"Cancer"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1164\/arrd.1983.127.5.659","article-title":"Medical section of the American Lung Association. Clinical staging of primary lung cancer","volume":"127","year":"1983","journal-title":"Am Rev Respir Dis"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0169-5002(02)00513-5","article-title":"Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer","volume":"39","author":"JL Pujol","year":"2003","journal-title":"Lung Cancer"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1097\/JTO.0b013e318290868f","article-title":"Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology","volume":"8","author":"NI Lindeman","year":"2013","journal-title":"J Thorac Oncol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1097\/IGC.0b013e3182681cfd","article-title":"The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients","volume":"22","author":"KD Steffensen","year":"2012","journal-title":"Int J Gynecol Cancer"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1515\/cclm-2012-0097","article-title":"Human epididymis protein 4 (HE4) in benign and malignant diseases","volume":"50","author":"L Hertlein","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0169-5002(00)00186-0","article-title":"Cyfra 21\u20131, neuron specific enolase and prognosis of non-small cell lung cancer: prospective study in 621 patients","volume":"31","author":"JL Pujol","year":"2001","journal-title":"Lung Cancer"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0128836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T22:54:09Z","timestamp":1599087249000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0128836"}},"subtitle":[],"editor":[{"given":"Ramon Andrade","family":"de Mello","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,6,1]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0128836","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,1]]}}}