Of the differentially expressed proteins, CO9, LBP, SVEP1, and VWF were the best candidate liquid biopsy biomarkers for diagnosing CHB, as their levels were increased in serum EVs (sEVs) and presented higher area under the curve (AUC) values of 0.925 (1.000/0.929), 0.950 (0.964/0.964), 0.900 (1.000/1.000), and 0.875 (1.000/0.964), respectively, in patients with LC and HCC compared with those of HCs (Fig. 5a–c). This evidence concerns the gene LBP and laryngotracheoesophageal cleft.