Lin Hai, Jiao Xuelong, Yu Benxia, Du Jiangdong, Xu HaiYan, Dong Aiping, Wan Chunsheng
Department of Gastroenterology, The Central Hospital of Linyi, Yishui, Shandong, China.
Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Cancer Biomark. 2017 Aug 23;20(2):143-150. doi: 10.3233/CBM-160533.
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.
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.
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.
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.
14-3-3家族是一类保守的调节蛋白，包括β（β）、γ（γ）、ζ（ζ）、σ（ε）、τ（η）和δ（σ）等亚型，在肝细胞癌（HCC）中过表达，且与转移风险高和生存率低相关。在本研究中，我们调查了血清14-3-3亚型是否与HCC进展及患者生存相关。
收集了2006年1月至2010年12月期间63例行手术切除的HCC患者、104例接受非手术抗HCC治疗的患者、50例单纯肝硬化患者、45例单纯慢性肝炎患者及50例健康受试者的血清样本。采用酶联免疫吸附测定法（ELISA）检测血清中14-3-3（β、ε、γ、σ和ζ）亚型的水平。通过逻辑回归分析检验14-3-3（β和σ）亚型与临床病理因素之间的相关性。采用ROC曲线分析评估血清14-3-3β鉴别HCC患者的可行性。通过Kaplan-Meier分析和Cox回归模型进行患者生存分析。
HCC患者血清中14-3-3（β和σ）水平显著高于肝硬化、慢性肝炎患者及健康受试者（p<0.05）。HCC患者与其他组之间14-3-3ε、γ和ζ的血清水平无差异（p>0.05）。血清14-3-3β水平高与血管侵犯（p=0.016）、TNM分期（p=0.012）、BCLC分期（p=0.01）及早期复发（p=0.013）相关。血清14-3-3β水平高的患者预后较差。14-3-3σ水平与临床病理参数之间无显著关联。单因素和多因素分析均显示血清14-3-3β与HCC之间存在显著独立关联（p<0.05）。血清14-3-3β在截断值为18.7 ng/mL时可有效鉴别HCC患者，敏感性为91.4%，特异性为75.3%。
血清14-3-3β是早期HCC诊断的潜在生物标志物，血清14-3-3β水平高与HCC转移及预后不良相关。
