Plasma Anti-PRTN3 IgG and IgM Autoantibodies: Novel Biomarkers for Early Detection of Lung Adenocarcinoma

Yutong Li ^1,2,3 Linhong Wang ^1,2,3 Fengqi Chen ^1,2,3 Rulan Liao ^1,2,3 Jing Li ^1,2,3 Xiaobin Cao ^1,2,3 Liping Dai ^1,2,3,4,5* Renle Du ^1,2,3,6*

• ¹ Zhengzhou University, Zhengzhou, China
• ² Henan Academy of Medical and Pharmaceutical Sciences, Institute of Medicine, Zhengzhou University, Zhengzhou, Henan Province, China
• ³ BGI College, Zhengzhou University, Zhengzhou, China, Zhengzhou, Henan Province, China
• ⁴ Henan Provincial Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan Province, China
• ⁵ State Key Laboratory for the Prevention and Treatment of Esophageal Cancer, Zhengzhou University, Zhengzhou, Henan Province, China
• ⁶ Henan Provincial Key Laboratory of Hepatology Pharmacology, Zhengzhou, Henan Province, China

Background: Proteinase 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.Methods: Immunohistochemistry 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.Results: PRTN3 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.Anti-PRTN3 IgG and IgM autoantibodies maybe early biomarkers to differentiate LUAD from NC and BPN.