Hai Lin1, Xuelong Jiao2, Benxia Yu2, Jiangdong Du1,3, HaiYan Xu4, Aiping Dong5, Chunsheng Wan3. 1. Department of Gastroenterology, The Central Hospital of Linyi, Yishui, Shandong, China. 2. Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. 3. Department of Clinical Laboratory, Yantaiyuhuangding Hospital, Yantai, Shandong, China. 4. Department of Hemopurification Center, Yantaiyuhuangding Hospital, Yantai, Shandong, China. 5. Department of Clinical Laboratory, People's Hospital of Weifang, Weifang, Shandong, China.
Abstract
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.
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.
Entities:
Keywords:
14-3-3 family proteins; Hepatocellular carcinoma; prognosis