Clinical significance of serum 14-3-3 beta in patients with hepatocellular carcinoma

Objective: The 14-3-3 family of conserved regulatory proteins comprises the isoforms beta (β), gamma (γ), zeta (ζ), sigma (ε), tau (η), and delta (σ), which are overexpressed and associated with a high risk of metastasis and poor survival in hepatocellular carcinoma (HCC). In the present study, we investigated whether serum 14-3-3 isoforms are related to HCC progression and patient survival.

Methods: Serum samples from 63 HCC patients who underwent surgical reSection 104 HCC patients who received non-surgical anti-HCC treatments, 50 patients with liver cirrhosis alone, 45 patients with chronic hepatitis alone, and 50 healthy subjects were collected between January 2006 and December 2010. Serum levels of 14-3-3 (β, ε, γ, σ, and ζ) isoforms were measured by ELISA. The correlation between 14-3-3 (β and σ) isoforms and clinicopathological factors was examined by logistic regression analysis. The feasibility of serum 14-3-3 β for discriminating HCC patients was assessed by ROC curve analysis. Patient survival analyses were performed by Kaplan-Meier analyses and Cox regression models.

Results: Serum levels of 14-3-3 (β and σ) were significantly higher in HCC patients than in those with liver cirrhosis, chronic hepatitis, and healthy subjects (p< 0.05). There was no difference in the serum levels of 14-3-3 ε, γ, and ζ between HCC and the other groups (p> 0.05). High levels of serum 14-3-3 β were associated with vascular invasion (p= 0.016), TNM stage (p= 0.012), BCLC stage (p= 0.01), and early recurrence (p= 0.013). Patients with high levels of serum 14-3-3 β had a poor prognosis. There was no significant association between 14-3-3 σ levels and clinicopathological parameters. A significant independent association between serum 14-3-3 β and HCC was observed by univariate and multivariate analysis (p< 0.05). Serum 14-3-3 β could effectively discriminate HCC patients at a cut-off point of 18.7 ng/mL, with 91.4% sensitivity and 75.3% specificity.

Conclusions: Serum 14-3-3 β is a potential biomarker for the diagnosis of early-stage HCC, and high levels of serum 14-3-3 β were associated with metastasis and poor prognosis in HCC.