AUTHOR=Cao Xiaobin , Li Jing , Liu Siyu , Liu Aichen , Zhang Lulu , Chen Fengqi , Li Yutong , Ma Hanke , Sun Wenke , Ouyang Songyun , Dai Liping , Liu Jingjing 

TITLE=Plasma IgG and IgM autoantibodies to COPT1 as potential biomarkers for detection of non-small cell lung cancer

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1455095

DOI=10.3389/fimmu.2025.1455095

ISSN=1664-3224

ABSTRACT=BackgroundEarly 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).MethodsThe 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.ResultsBased 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 (P<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.ConclusionsOur 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.