Expression of Fibroblast Growth Factor 19 Is Associated with Recurrence and Poor Prognosis of Hepatocellular Carcinoma

Abstract

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.