{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:23:57Z","timestamp":1791919437859,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Early diagnosis of lung cancer is crucial for improving patient outcomes. Autoantibodies against tumor-associated antigens (TAAs) found in the plasma can serve as biomarkers for lung cancer detection. Copper transporter 1 (COPT1) is abnormally expressed in several cancers including lung cancer. The purpose of this study is to explore the significance of anti-COPT1 autoantibodies in the clinical diagnosis of non-small cell lung cancer (NSCLC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression level of COPT1 in NSCLC and normal tissues was analyzed based on TCGA and the Human Protein Atlas (HPA) database. Through enzyme-linked immunosorbent assay (ELISA), the expression levels of anti-COPT1 autoantibodies in plasma samples from normal controls (NC), patients with benign pulmonary nodules (BPN), and patients with NSCLC were detected in the discovery (89 NC and 89 NSCLC) and verification (321 NC, 321 BPN and 321 NSCLC) groups. The ELISA results were verified by western blotting and indirect immunofluorescence experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on HPA and TCGA databases, the mRNA and protein levels of COPT1 were higher in NSCLC tissues than in normal tissues. The levels of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies were significantly higher in patients with NSCLC (<jats:italic>P<\/jats:italic>&amp;lt;0.05). Anti-COPT1-IgG and anti-COPT1-IgM could discriminate NSCLC from NC with area under the curve (AUC) values of 0.733 (95% CI: 0.694-0.771) and 0.679 (95% CI: 0.638-0.720), respectively. Additionally, the combination of anti-COPT1-IgG, anti-COPT1-IgM, and carcinoembryonic antigen (CEA) could enhance the efficacy of NSCLC diagnosis from BPN with increased AUC values.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study indicated the potential significance of anti-COPT1-IgG and anti-COPT1-IgM autoantibodies as novel biomarkers for the detection of NSCLC. Furthermore, the combination of anti-COPT1-IgG and anti-COPT1-IgM improved the diagnostic value.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1455095","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:15:13Z","timestamp":1744348513000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasma IgG and IgM autoantibodies to COPT1 as potential biomarkers for detection of non-small cell lung cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaobin","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aichen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanke","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenke","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyun","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global\u00a0cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60735-0","article-title":"Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship","volume":"83","author":"Molina","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"B3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3322\/CA.2007.0010","article-title":"Cancer statistics, 2008","volume":"58","author":"Jemal","year":"2008","journal-title":"CA Cancer J Clin"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8661","DOI":"10.3390\/ijms22168661","article-title":"Current and future development in lung cancer diagnosis","volume":"22","author":"Nooreldeen","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i19.3496","article-title":"Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of \u03b1-fetoprotein-negative hepatocellular carcinoma","volume":"23","author":"Wang","year":"2017","journal-title":"World J Gastroenterol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4472-1","article-title":"A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with cervical cancer","volume":"37","author":"Huangfu","year":"2016","journal-title":"Tumor Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00163","article-title":"Past, present, and future of rituximab-the world\u2019s first oncology monoclonal antibody therapy","volume":"8","author":"Pierpont","year":"2018","journal-title":"Front Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.626616","article-title":"Bispecific antibodies: from research to clinical application","volume":"12","author":"Ma","year":"2021","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.658922","article-title":"Discovering panel of\u00a0autoantibodies for early detection of lung cancer based on focused protein array","volume":"12","author":"Jiang","year":"2021","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-0459","article-title":"The impact of autoimmune diseases on the incidence and prognosis of cutaneous Malignant melanoma","volume":"16","author":"Kaae","year":"2007","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8582-0","article-title":"High prevalence of neuronal surface autoantibodies associated with cognitive deficits in cancer patients","volume":"264","author":"Finke","year":"2017","journal-title":"J Neurology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318215a0a4","article-title":"Clinical relevance of autoantibody detection in lung cancer","volume":"6","author":"Solassol","year":"2011","journal-title":"J Thorac Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70360-9","article-title":"p53 Antibodies in the sera of patients with various types of cancer: a review","volume":"60","author":"Soussi","year":"2000","journal-title":"Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.2388","article-title":"Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera","volume":"26","author":"Qiu","year":"2008","journal-title":"J Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.240523","article-title":"Dynamic and cell-specific transport networks for intracellular copper ions","volume":"134","author":"Lutsenko","year":"2021","journal-title":"J Cell Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004303","article-title":"Copper promotes\u00a0tumorigenesis by activating the PDK1-AKT oncogenic pathway in a copper transporter 1 dependent manner","volume":"8","author":"Guo","year":"2021","journal-title":"Adv Sci (Weinh)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.05.033","article-title":"A SLC31A1-MEK-DNMT1-miR-124 feedback loop contributes to pancreatic cancer progression","volume":"10","author":"Jin","year":"2023","journal-title":"Genes Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101125","DOI":"10.1016\/j.neo.2025.101125","article-title":"SLC31A1 promotes chemoresistance through inducing CPT1A-mediated fatty acid oxidation in ER-positive breast cancer","volume":"61","author":"Li","year":"2025","journal-title":"Neoplasia"},{"key":"B20","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s12920-023-01489-9","article-title":"Systematic pan-cancer analysis identifies SLC31A1 as a biomarker in multiple tumor types","volume":"16","author":"Kong","year":"2023","journal-title":"BMC Med Genomics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.240523","article-title":"Cuproptosis-related gene SLC31A1 is a potential predictor for diagnosis, prognosis and therapeutic response of breast cancer","volume":"12","author":"Li","year":"2022","journal-title":"Am J Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00611.x","article-title":"Autoantibodies to tumor-associated antigens: reporters from the immune system","volume":"222","author":"Tan","year":"2008","journal-title":"Immunol Rev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s13063-023-07285-1","article-title":"How to reach agreement: the impact of different analytical approaches to Delphi process results in core outcomes set development","volume":"24","author":"Webbe","year":"2023","journal-title":"Trials"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032695","article-title":"Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1097\/JTO.0000000000000405","article-title":"Molecularly targeted therapies in non-small-cell lung cancer annual update 2014","volume":"10","author":"Morgensztern","year":"2015","journal-title":"J\u00a0Thorac Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2011.11.012","article-title":"Carcinoembryonic antigen (CEA) as tumor marker\u00a0in\u00a0lung cancer","volume":"76","author":"Grunnet","year":"2012","journal-title":"Lung Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1159\/000224628","article-title":"Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer: correlation with histology","volume":"30","author":"Molina","year":"2009","journal-title":"Tumour Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2011.03.019","article-title":"Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC)","volume":"12","author":"Cedr\u00e9s","year":"2011","journal-title":"Clin Lung Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.97.10030603","article-title":"Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis","volume":"10","author":"Pastor","year":"1997","journal-title":"Eur Respir J"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2013.01.002","article-title":"Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer","volume":"80","author":"Okamura","year":"2013","journal-title":"Lung Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s13075-017-1380-3","article-title":"Emerging technologies in autoantibody testing for rheumatic diseases","volume":"19","author":"Olsen","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.12.032","article-title":"Novel neuronal autoantibodies in huntington\u2019s disease","volume":"91","author":"Endres","year":"2022","journal-title":"Biol Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2021-0374","article-title":"Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes","volume":"17","author":"Jiang","year":"2022","journal-title":"Nanomedicine (Lond)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"103558","DOI":"10.1016\/j.ebiom.2021.103558","article-title":"ZNF711 down-regulation promotes CISPLATIN resistance in epithelial ovarian cancer via interacting with JHDM2A and suppressing SLC31A1 expression","volume":"71","author":"Wu","year":"2021","journal-title":"EBioMedicine"},{"key":"B35","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/s41420-022-00872-2","article-title":"YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis","volume":"8","author":"Zhang","year":"2022","journal-title":"Cell Death Discovery"},{"key":"B36","first-page":"7995","article-title":"Natural IgM antibodies and immunosurveillance mechanisms against epithelial cancer cells in humans","volume":"63","author":"Br\u00e4ndlein","year":"2003","journal-title":"Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.3390\/biomedicines11112884","article-title":"SLC31A1 identifying a novel biomarker with potential prognostic and immunotherapeutic potential in pan-cancer","volume":"11","author":"Zhang","year":"2023","journal-title":"Biomedicines"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0471","article-title":"Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion","volume":"80","author":"Voli","year":"2020","journal-title":"Cancer Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1186\/s12859-022-04894-6","article-title":"High expression of cuproptosis-related SLC31A1 gene in relation to unfavorable outcome and deregulated immune cell infiltration in breast cancer: an analysis based on public databases","volume":"23","author":"Li","year":"2022","journal-title":"BMC Bioinf"},{"key":"B40","doi-asserted-by":"publisher","first-page":"17790","DOI":"10.1038\/s41598-023-44681-8","article-title":"Cuproptosis-related gene SLC31A1: prognosis values and potential biological functions in cancer","volume":"13","author":"Qi","year":"2023","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1310359","article-title":"Identification of autoantibodies to ECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer","volume":"6","author":"Dai","year":"2017","journal-title":"Oncoimmunology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182356","article-title":"BARD1 serum autoantibodies for the detection of lung cancer","volume":"12","author":"Pilyugin","year":"2017","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1138200","article-title":"Serum anti-MDM2 and anti-c-Myc autoantibodies as biomarkers in the early detection of lung cancer","volume":"5","author":"Li","year":"2016","journal-title":"Oncoimmunology"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095444","article-title":"Development of a multiplex autoantibody test for detection of lung cancer","volume":"9","author":"Jia","year":"2014","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"151891","DOI":"10.1016\/j.imbio.2019.11.026","article-title":"Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer","volume":"225","author":"Pei","year":"2020","journal-title":"Immunobiology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.728853","article-title":"A diagnostic model with igM autoantibodies and carcinoembryonic antigen for early detection of lung adenocarcinoma","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1455095\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:15:14Z","timestamp":1744348514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1455095\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1455095"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1455095","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"article-number":"1455095"}}