Anti-FDX1 Autoantibody as a Potential Biomarker for Non–Small Cell Lung Cancer Detection

Abstract Background: Autoantibodies can be readily identified prior to biopsy and may serve as valuable biomarkers for cancer detection. Ferredoxin 1 (FDX1) is a key regulator in the process of cuproptosis and affects the prognosis of lung cancer. In this study, we investigated whether the anti-FDX1 autoantibody could serve as a novel biomarker for the detection of non–small cell lung cancer (NSCLC). Methods: A total of 1,155 plasma samples were divided into the verification and validation groups. The expression levels of the anti-FDX1 autoantibody in 414 patients with NSCLC, 327 patients with benign pulmonary nodules (BPN), and 414 normal controls (NC) were detected using ELISA. Western blotting and immunofluorescence analyses were performed to confirm the ELISA results. Results: Plasma anti-FDX1 autoantibody levels were significantly higher in patients with NSCLC than in patients with BPN and NCs in the verification and validation groups. The ELISA results were confirmed by Western blotting and immunofluorescence. The anti-FDX1 autoantibody distinguished NSCLC from NC and BPN with an AUC (95% confidence interval) of 0.806 (0.772–0.839) and 0.627 (0.584–0.670), respectively. Conclusions: Our study demonstrated the potential benefits of the anti-FDX1 autoantibody as a novel biomarker for NSCLC detection. Impact: These findings suggested that the anti-FDX1 autoantibody may facilitate the detection of NSCLC.