{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T20:45:45Z","timestamp":1783025145084,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Serum biomarkers have been widely adopted in clinical practice for assisting lung cancer diagnoses, therapeutic monitoring, and prognostication. The function of a well\u2010performing tumor biomarker depends on a reliable reference interval (RI) with consideration of the study subjects\u2019 age, gender, and geographical location. This study aimed to establish a RI for each of 6 lung cancer biomarkers for use in the whole country of China on Mindray platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The levels of serum 6 lung cancer biomarkers\u2014namely progastrin\u2010releasing peptide (ProGRP), neuron\u2010specific enolase (NSE), squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin\u201019 fragment (CYFRA21\u20101), and human epididymis protein 4 (HE4)\u2014were measured utilizing the chemiluminescence immunoassay on the Mindray CL\u20106000i platform following the laboratory standard operating procedures in apparently healthy Chinese individuals on large cohort, multicenter, and geographical consideration bases. The CLSI EP28\u2010A3C guideline was followed for the enrollment of study subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The age\u2010stratified, gender\u2010specific RIs for ProGRP, NSE, SCC, CEA, CYFRA21\u20101, and HE4 lung cancer biomarkers in the Chinese population have been established as described in the results and discussion in this work. In addition, various levels of the six lung cancer biomarkers among nine geographical locations in China have been observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The sample volume of study cohort, age, and geographical location should be considered upon establishing a reliable biomarker RI. A RI for each of six lung cancer biomarkers has been established. The results from this study would be helpful for clinical laboratories in interpreting the analytical results and for clinicians in patient management.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.23816","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T06:24:10Z","timestamp":1620887050000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Age\u2010stratified and gender\u2010specific reference intervals of six tumor markers panel of lung cancer: A geographic\u2010based multicenter study in China"],"prefix":"10.1002","volume":"35","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-3780","authenticated-orcid":false,"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The First Affiliated Hospital of University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radio Immunoassay Center Shaanxi Provincial People\u2019s Hospital  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital  Chengdou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Suzhou Municipal Hospital  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Henan Provincial People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of in vitro Diagnostics Shenzhen Mindray Bio\u2010Medical Electronics Corporation  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of in vitro Diagnostics Shenzhen Mindray Bio\u2010Medical Electronics Corporation  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of in vitro Diagnostics Shenzhen Mindray Bio\u2010Medical Electronics Corporation  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-2587","authenticated-orcid":false,"given":"Shukui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"liang Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology Fourth Military Medical University  Xi\u2019an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-0838","authenticated-orcid":false,"given":"Huayi","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of in vitro Diagnostics Shenzhen Mindray Bio\u2010Medical Electronics Corporation  Shenzhen China"},{"name":"Department of Surgical Oncology Roswell Park Comprehensive Cancer Center  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"https:\/\/cancerprogressreport.aacr.org\/progress\/"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40880-019-0368-6"},{"key":"e_1_2_9_4_1","unstructured":"https:\/\/gco.iarc.fr\/today\/data\/factsheets\/populations\/160\u2010china\u2010fact\u2010sheets.pdf"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-019-02086-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1177271917751608"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2018.12.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13019-020-01353-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13585"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01173"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/crj.13242"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2082840"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-190840"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.02.017"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.2078"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.01.079"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01557-z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-020-01894-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20192732"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2011.11.012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2016.02.002"},{"issue":"9","key":"e_1_2_9_23_1","first-page":"1421","article-title":"Serum human epididymis secretory protein 4 (HE4) is a potential prognostic biomarker in non\u2010small cell lung cancer","volume":"64","author":"Mo D","year":"2018","journal-title":"Clin Lab"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/352670"},{"key":"e_1_2_9_25_1","volume-title":"Establishing, and verifying reference intervals in the clinical laboratory; approved guideline","author":"Defining CLSI","year":"2010"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22863"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365513.2018.1555855"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1724600818776828"},{"issue":"6","key":"e_1_2_9_29_1","first-page":"923","article-title":"Age and gender\u2010specific reference intervals for ProGRP in healthy Chinese Han Ethnic Adults using the Roche Cobas Immunoassay","volume":"64","author":"Zhu Y","year":"2018","journal-title":"Clin Lab"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22997"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(96)06278-X"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.08.019"},{"issue":"3","key":"e_1_2_9_33_1","first-page":"1773","article-title":"Pro\u2010gastrin\u2010releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21\u20131 and NSE in patients with lung cancer","volume":"25","author":"Molina R","year":"2005","journal-title":"Anticancer Res"},{"issue":"7","key":"e_1_2_9_34_1","first-page":"11295","article-title":"Diagnostic value of Cyfra21\u20101, SCC and CEA for differentiation of early\u2010stage NSCLC from benign lung disease","volume":"8","author":"Chen F","year":"2015","journal-title":"Int J Clin Exp Med"}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.23816","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.23816","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.23816","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T19:30:30Z","timestamp":1693423830000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.23816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/jcla.23816"],"URL":"https:\/\/doi.org\/10.1002\/jcla.23816","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"value":"0887-8013","type":"print"},{"value":"1098-2825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"2021-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23816"}}