Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Dig Dis Sci. 2013 Jul;58(7):1916-22. doi: 10.1007/s10620-013-2609-x. Epub 2013 Mar 2.
Fibroblast growth factor 19 (FGF19)-mediated activation of mitogen-activated protein kinase and the β-catenin pathway may be involved in the development and progression of hepatocellular carcinoma. This study aimed to elucidate the prognostic significance of FGF19 protein expression in hepatocellular carcinoma patients.
By immunohistochemistry, we investigated the expression of FGF19 protein in tumor tissue from 281 hepatocellular carcinoma patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 75.6 months.
FGF19 protein expression was observed in 135 (48.0 %) of the 281 hepatocellular carcinomas. FGF19 expression was significantly associated with larger tumor size (P < 0.001), and higher BCLC stage (P = 0.001). FGF19 expression was correlated with the early recurrence (P < 0.001), but not with the late recurrence (P = 0.582). FGF19 expression (P = 0.002), viral etiology (P = 0.028), and intrahepatic metastasis (P < 0.001) were independent predictors of early recurrence. Multivariate analyses of survival revealed that FGF19 expression (P < 0.001), intrahepatic metastasis (P < 0.001), and liver cirrhosis (P = 0.019) were independent predictors of shorter disease-free survival. FGF19 expression (P = 0.005), larger tumor size (P = 0.038), major portal vein invasion (P = 0.048), intrahepatic metastasis (P < 0.001), lower albumin level (P = 0.024), and liver cirrhosis (P = 0.031) were independent predictors of shorter disease-specific survival.
FGF19 protein expression might be an effective predictor of early recurrence and a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy, indicating that FGF19 might be a potential preventive target in hepatocellular carcinoma patients.
成纤维细胞生长因子 19（FGF19）介导的丝裂原活化蛋白激酶和β-连环蛋白途径的激活可能参与了肝细胞癌的发展和进展。本研究旨在阐明 FGF19 蛋白表达在肝细胞癌患者中的预后意义。
通过免疫组织化学方法，我们检测了 281 例接受根治性肝切除术的肝细胞癌患者肿瘤组织中 FGF19 蛋白的表达。进行单因素和多因素分析以评估其对患者肿瘤复发和生存的预测价值。中位随访时间为 75.6 个月。
在 281 例肝细胞癌中，观察到 135 例（48.0%）存在 FGF19 蛋白表达。FGF19 表达与肿瘤较大（P<0.001）和较高的 BCLC 分期（P=0.001）显著相关。FGF19 表达与早期复发相关（P<0.001），但与晚期复发无关（P=0.582）。FGF19 表达（P=0.002）、病毒病因（P=0.028）和肝内转移（P<0.001）是早期复发的独立预测因素。生存的多因素分析显示，FGF19 表达（P<0.001）、肝内转移（P<0.001）和肝硬化（P=0.019）是无病生存时间较短的独立预测因素。FGF19 表达（P=0.005）、肿瘤较大（P=0.038）、主门静脉侵犯（P=0.048）、肝内转移（P<0.001）、低白蛋白水平（P=0.024）和肝硬化（P=0.031）是疾病特异性生存时间较短的独立预测因素。
FGF19 蛋白表达可能是肝细胞癌根治性肝切除术后早期复发的有效预测因子，也是预后不良的标志物，提示 FGF19 可能是肝细胞癌患者的一个潜在预防靶点。
