Gong Xue-Yi, Ma Ning, Xu Hong-Xu, Chen Fan, Huang Xiao-Hui, Wang Qian
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of General Surgical Laboratory, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Oncol Lett. 2018 Mar;15(3):3796-3805. doi: 10.3892/ol.2018.7733. Epub 2018 Jan 5.
The present study aimed to investigate the prognostic value of specific molecular markers in patients with hepatocellular carcinoma (HCC) who had received surgery. Immunohistochemical analysis was used to measure the expression of hepatocyte growth factor receptor (c-Met), β-catenin and focal adhesion kinase (FAK) in patients with HCC. c-Met expression was identified to be high in patients with larger tumors, higher α-fetoprotein (AFP) levels, higher Edmondson grades, portal vein invasion and higher tumor-node-metastasis (TNM) stages. FAK expression was high in patients with portal vein invasion, higher Edmondson grades and higher TNM stages. β-catenin expression was high in patients with larger tumors, hepatitis B virus (HBV) infection, portal vein invasion, higher Edmondson grades and higher TNM stages. Following multivariate analysis, FAK (P=0.002) and β-catenin (P=0.006) expression levels were demonstrated to be significantly associated with Edmondson grade. Additionally, the tumor size (P=0.009) and HBV infection status (P=0.002) were revealed to be associated with β-catenin expression. Kaplan-Meier survival curve analysis demonstrated that patients with HCC with higher FAK expression, higher β-catenin expression, portal vein invasion, higher Edmondson grades, higher TNM stages, younger ages and higher AFP levels had significantly poorer prognoses. Cox's regression analysis revealed that the survival period was correlated with the Edmondson grade, age, AFP level, and FAK and β-catenin expression. Univariate analysis of c-Met, β-catenin and FAK identified a significant correlation between FAK and β-catenin (P=0.015). Correlation analysis revealed no significant correlation between the three molecular markers, but β-catenin and c-Met were markedly correlated (P=0.052). No significant correlation between FAK, c-Met or β-catenin expression was identified. FAK and β-catenin expression demonstrated a correlation with a range of clinicopathological factors, and high FAK and β-catenin expression levels were identified to be correlated with a poor survival rate of patients with HCC. Thus, patients with higher FAK and β-catenin expression may require more aggressive therapy. The results of the present study suggest that FAK and β-catenin expression possess more prognostic value than c-Met expression in patients with HCC.
本研究旨在探讨特定分子标志物在接受手术的肝细胞癌(HCC)患者中的预后价值。采用免疫组织化学分析方法检测HCC患者中肝细胞生长因子受体(c-Met)、β-连环蛋白和粘着斑激酶(FAK)的表达。结果发现,肿瘤较大、甲胎蛋白(AFP)水平较高、Edmondson分级较高、存在门静脉侵犯以及肿瘤-淋巴结-转移(TNM)分期较高的患者c-Met表达较高。存在门静脉侵犯、Edmondson分级较高及TNM分期较高的患者FAK表达较高。肿瘤较大、感染乙型肝炎病毒(HBV)、存在门静脉侵犯、Edmondson分级较高及TNM分期较高的患者β-连环蛋白表达较高。多因素分析显示,FAK(P=0.002)和β-连环蛋白(P=0.006)表达水平与Edmondson分级显著相关。此外,肿瘤大小(P=0.009)和HBV感染状态(P=0.002)与β-连环蛋白表达相关。Kaplan-Meier生存曲线分析表明,FAK表达较高、β-连环蛋白表达较高、存在门静脉侵犯、Edmondson分级较高、TNM分期较高、年龄较小及AFP水平较高的HCC患者预后明显较差。Cox回归分析显示,生存期与Edmondson分级、年龄、AFP水平以及FAK和β-连环蛋白表达相关。对c-Met、β-连环蛋白和FAK进行单因素分析发现,FAK与β-连环蛋白之间存在显著相关性(P=0.015)。相关性分析显示,这三种分子标志物之间无显著相关性,但β-连环蛋白与c-Met显著相关(P=0.052)。未发现FAK、c-Met或β-连环蛋白表达之间存在显著相关性。FAK和β-连环蛋白表达与一系列临床病理因素相关,且FAK和β-连环蛋白高表达与HCC患者生存率低相关。因此,FAK和β-连环蛋白表达较高的患者可能需要更积极的治疗。本研究结果表明,在HCC患者中,FAK和β-连环蛋白表达比c-Met表达具有更高的预后价值。