Plasma exosomes contain protein biomarkers valuable for the diagnosis of lung cancer

Abstract Accumulating evidence indicates that exosomal proteins are critical in diagnosing malignant tumors. To identify novel exosomal biomarkers for lung cancer diagnosis, we isolated plasma exosomes from 517 lung cancer patients and 168 healthy controls (NLs)—186 lung adenocarcinoma (LUAD) patients (screening (SN): 20, validation (VD): 166), 159 lung squamous carcinoma (LUSC) patients (SN: 20, VD: 139), 172 benign nodules (LUBN) patients (SN: 20, VD: 152) and 168 NLs (SN: 20, VD: 148)—and randomly assigned them to the SN or VD group. Proteomic analysis by LC–MS/MS and PRM were performed on all groups. The candidate humoral markers were evaluated and screened by a machine learning method. All selected biomarkers were identified in the VD groups. For LUAD, a 7-protein panel had AUCs of 97.9% and 87.6% in the training and test sets, respectively, and 89.5% for early LUAD. For LUSC, an 8-protein panel showed AUCs of 99.1% and 87.0% in the training and test sets and 92.3% for early LUSC. For LUAD + LUSC (LC), an 8-protein panel showed AUCs of 85.9% and 80.3% in the training and test sets and 87.1% for early LC diagnosis. The characteristics of the exosomal proteome make exosomes potential diagnostic tools.