Validation of a High-Specificity Blood Autoantibody Test to Detect Lung Cancer in Pulmonary Nodules

BACKGROUND: Pulmonary nodules (PNs) are frequently detected by chest CT scan, which is increasingly used in clinical practice. Accurately identifying malignant nodules can pose a diagnostic challenge; therefore, a high-specificity biomarker could help clinicians identify malignant nodules and ideally lead to the earlier diagnosis of lung cancer. RESEARCH QUESTION: What are the performance characteristics of a blood-based biomarker for identifying malignancy in patients with a CT-detected PN? STUDY DESIGN AND METHODS: Banked plasma samples from 2 independent prospective observational cohorts of patients presenting with benign or malignant PNs 8 to 30 mm in size were tested using a 7-autoantibody panel. Sensitivity, specificity, and positive predictive value of the autoantibody test (AAT) to identify cancer were calculated for the individual and combined cohorts. RESULTS: < .001). INTERPRETATION: This study validates the specificity of a blood-based autoantibody biomarker for identifying malignancy in patients with indeterminate PNs. This rule-in biomarker may help to expedite workup of malignant nodules. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov CHEST Pulmonary 2025; 3(1):100130.