AUTHOR=Li Yutong , Wang Linhong , Chen Fengqi , Liao Rulan , Li Jing , Cao Xiaobin , Ouyang Songyun , Dai Liping , Du Renle TITLE=Plasma anti-PRTN3 IgG and IgM autoantibodies: novel biomarkers for early detection of lung adenocarcinoma JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1534078 DOI=10.3389/fimmu.2025.1534078 ISSN=1664-3224 ABSTRACT=BackgroundProteinase 3 (PRTN3) has been recognized as a crucial target for anti-neutrophil cytoplasmic autoantibody. However, the relationship between anti-PRTN3 autoantibody and cancer remains largely unexplored.MethodsImmunohistochemistry was used to detect the level of PRTN3 in lung adenocarcinoma (LUAD) tissue array. Enzyme-linked immunosorbent assay was conducted to measure anti-PRTN3 IgG and IgM autoantibodies in plasma from patients with early- and advanced-stage LUAD, benign pulmonary nodules (BPN) and normal control (NC). Western blotting and immunofluorescence staining were performed to confirm the presence of plasma immune response to PRTN3.ResultsPRTN3 protein was highly expressed in LUAD tissues. Elevated plasma levels of anti-PRTN3 IgG and IgM autoantibodies were also detected in LUAD, especially in early LUAD. The AUC of anti-PRTN3 IgG autoantibodies in the diagnosis of early LUAD from NC was 0.782, and from BPN was 0.761. When CEA and anti-PRTN3 autoantibodies were combined, the AUC for the diagnosis of early LUAD was significantly higher than that of CEA alone. The presence of a plasma immune response to PRTN3 in LUAD was also confirmed.ConclusionAnti-PRTN3 IgG and IgM autoantibodies maybe early biomarkers to differentiate LUAD from NC and BPN.