An autoantibody signature targeting cuproptosis-related proteins for non-small cell lung cancer detection and prognosis

Background Autoantibodies against tumor-associated antigens in plasma are valuable biomarkers for early cancer detection and prognostic stratification. Dihydrolipoamide acetyltransferase (DLAT) and lipoic acid synthetase (LIAS), two key cuproptosis regulators, are abnormally expressed in non-small cell lung cancer (NSCLC) and are potential biomarkers for clinical diagnosis. This study explored the significance of anti-DLAT and anti-LIAS autoantibodies in the clinical diagnosis and prognosis of NSCLC. Methods Plasma levels of anti-DLAT and anti-LIAS autoantibodies were detected using Enzyme-Linked Immunosorbent Assay (ELISA). Their diagnostic value was evaluated in 340 cases with normal control (NC), 260 patients with benign pulmonary nodule (BPN) and 340 patients with NSCLC. Additionally, the prognostic value of these autoantibodies was analyzed in a separate independent cohort of 354 patients with NSCLC. Results The expression levels of anti-DLAT and anti-LIAS autoantibodies were significantly elevated in NSCLC compared to those in BPN and NC. These autoantibodies distinguished NSCLC from NC with AUCs of 0.712 (95% CI [0.669–0.756]) and 0.668 (95% CI [0.623–0.714]), respectively. To enhance diagnostic efficacy, a multi-autoantibody signature (anti-DLAT/LIAS/FDX1/COPT1) was constructed, which significantly improved discrimination (NSCLC vs NC: AUC = 0.805; NSCLC vs BPN: AUC = 0.751). Prognostic analysis indicated that anti-LIAS autoantibody served as an independent predictor of outcome (HR = 1.42, 95% CI [1.01–1.99]). Conclusions These findings demonstrate the clinical utility of an autoantibody signature targeting cuproptosis-related proteins for NSCLC diagnosis and prognosis.