Biomarkers of GPC3, DCP and VEGF in Hepatocellular Carcinoma: Early Diagnostic and Prognostic Significance in the Chinese Population

Abstract Background: Glypican-3 (GPC3), des-γ-carboxyprothrombin (DCP) and vascular endothelial growth factor (VEGF) are potential biomarkers for the early diagnosis and prognosis of hepatocellular carcinoma (HCC), especially in AFP negative patients. However, their sensitivity and accuracy as biomarkers are still needed to be compared and verified by large clinical samples in Chinese population. Methods: ELISA was used to evaluate the GPC3, DCP and VEGF in the serum of 136 HCC patients, 47 liver cirrhosis patients and 46 healthy controls. Meanwhile, the risk factors and mortality for HCC recurrence were also investigated to obtain some prognostic variables according to the histopathological evaluation and follow-up data. Results: The GPC3 and VEGF serum levels were significantly sensitive and specific compared with those of AFP and DCP for the diagnosis of HCC based on cut-off values. Compared with VEGF, the maximum area under the curve (AUC) of serum GPC3 level indicated most accurately in the diagnosis of HCC. In addition, GPC3 level was increased in 50.6% (39 / 77) of HCC patients with negative serum AFP. The risk factors for recurrence were high serum levels of tumor biomarkers, including DCP (>350 mAu/ml) and VEGF (>112 pg/ml) which were significantly higher in patients with microvascular invasion (MVI) than in those without MVI (P<0.01). Moreover, the expression of VEGF in various types of tumor invasion was also significantly different (P < 0.05, type 3 vs. type 1). Conclusions: Serum GPC3 and VEGF levels have the potential to be effective biomarkers for the early diagnosis of HCC, especially for these with normal serum AFP. Serum DCP and VEGF levels would be non-invasive prognostic biomarker substitute for tumor invasiveness and MVI, which were tightly correlated with postoperative recurrence of HCC.