{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:14:44Z","timestamp":1790759684526,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"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":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immunotherapy was widely used for the treatment of non\u2010small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples of 89\u00a0NSCLC patients and 57\u00a0healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta\u2010Plex Human Immuno\u2010Oncology Checkpoint Panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression levels of sTIM\u20103, sCD137, sCD27, sLAG\u20103, sIDO, sPD\u2010L2, sCD152, sCD80, and sPD\u20101 were all significantly increased in serum of NSCLC patients. Especially, sLAG\u20103 was significantly elevated in serum of NSCLC patients at early\u2010stage (stages I and II), TIM\u20103, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early\u2010stage groups. Receiver operating characteristics (ROC) results showed that except for PD\u20101, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM\u20103\u00a0had the highest diagnostic accuracy, followed by sLAG\u20103. Combining sTIM\u20103, sLAG\u20103, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM\u20103 and sIDO were correlated with stage and age, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TIM\u20103 and LAG\u20103 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM\u20103, LAG\u20103, and CD137 could increase the diagnostic accuracy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24224","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T10:40:03Z","timestamp":1641984003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A comprehensive profiling of soluble immune checkpoints from the sera of patients with non\u2010small cell lung cancer"],"prefix":"10.1002","volume":"36","author":[{"given":"Ying","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Liyang People\u2019s Hospital Liyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory Medicine Zhongda Hospital Southeast University Nanjing 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