Background. Autoantibodies against tumor-associated antigens in the plasma are valuable biomarkers for early cancer detection and prognostic stratification. DLAT (Dihydrolipoamide Acetyltransferase) and LIAS (Lipoic Acid Synthase), two key cuproptosis regulators, were abnormally expressed in non-small cell lung cancer (NSCLC) and are potential biomarkers for clinical diagnosis. This study aimed to explore the significance of anti-DLAT and anti-LIAS autoantibodies in the clinical diagnosis and prognosis of NSCLC.
Methods. The levels of plasma anti-DLAT and anti-LIAS autoantibodies were detected by ELISA. Their diagnostic value was evaluated in 340 NC (normal controls), 260 BPN (patients with benign pulmonary nodules), and 340 NSCLC. Additionally, the prognostic value of those autoantibodies was analyzed in 354 NSCLC patients.
Results. The levels of anti-DLAT and anti-LIAS autoantibodies were significantly elevated in NSCLC compared to BPN and NC. Those 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 efficacy, a multi-autoantibody signature (anti-DLAT/LIAS/FDX1/COPT1) was constructed, significantly improving 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 demonstrated the clinical utility of the autoantibody signature targeting cuproptosis-related proteins for NSCLC diagnosis and prognosis.
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