Integrative Multianalytical Model Based on Novel Plasma Protein Biomarkers for Distinguishing Lung Adenocarcinoma and Benign Pulmonary Nodules

Given the pressing clinical problem of making decision in diagnosis for subjects with pulmonary nodules, we aimed to discover novel plasma protein biomarkers for lung adenocarcinoma (LUAD) and benign pulmonary nodules (BPN), then develop an integrative multianalytical model to guide the clinical management of LUAD and BPN patients. Through label-free quantitative plasma proteomic analysis, twelve differentially expressed proteins (DEPs) in LUAD and BPN were screened. The diagnostic abilities of the DEPs were validated in two independent validation cohorts. The results showed that the level of three candidate proteins (PRDX2, PON1, APOC3) were lower in the plasma of LUAD than BPN. The three candidate proteins were combined with three promising computed tomography (CT) indicators (Spiculation, Vascular Notch Sign, Lobulation) and three traditional markers (CEA, CA125, CYFRA21-1) to construct an integrative multianalytical model, which was effective in distinguishing LUAD from BPN, with AUC of 0.904, sensitivity of 81.44% and specificity of 90.14%. Moreover, the model possessed impressive diagnostic performance between early LUADs and BPNs, with the AUC, sensitivity, specificity and accuracy of 0.868, 65.63%, 90.14% and 82.52%, respectively. This model maybe a useful auxiliary diagnostic tool for LUAD and BPN by achieving a better balance of sensitivity and specificity.