Abstract 3131: Expression of FGF19/FGFR4 related biomarkers in hepatocellular carcinoma

Abstract

Abstract Background: Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signaling play critical roles in hepatocarcinogenesis. This study explored the expression and clinical significance of FGF19/FGFR4 related signaling molecules in hepatocellular carcinoma (HCC). Method: We examined the mRNA expression of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1), and FGF4 in 151 surgically resected, primary unifocal HCC using quantitative real-time PCR analysis. The correlation of gene amplification and mRNA overexpression for FGF19 and FGF4 was investigated using a real-time PCR based copy number assay. FGF19 amplification was verified using fluorescence in situ hybridization. Univariate and multivariate analyses were performed to evaluate the prognostic value of these biomarkers for tumor recurrence and survival of patients. Results: Overexpression of FGF19, FGFR4, KLB, CCND1, and FGF4 mRNA was detected in 40%, 32%, 26%, 15%, and 35% of 151 tumors, respectively. In multivariate analyses, large tumor size (> 12.7 cm) and advanced tumor stage (stage ≥ II) independently predict worse patient survival. Using generalized additive models, we found mRNA expression of FGFR4 and KLB was significantly associated large tumor size (> 12.7 cm); mRNA expression of FGF19 and KLB was significantly associated advanced tumor stage (stage ≥ II). Furthermore, gene amplification of FGF19 and FGF4 significantly correlated to their mRNA overexpression (P = 0.006 for FGF19; P = 0.039 for FGF4). Conclusions: Overexpression of FGF19/FGFR4 related biomarkers is frequently found in HCC. Overexpression of FGF19 and FGF4 mRNA significantly correlates to their gene amplification. Expression status of FGFR4, KLB, and FGF19 may determine patient survival through their impact on tumor size (FGFR4 and KLB) and tumor stage (FGF19 and KLB). Citation Format: Zhong-Zhe Lin, Yung-Ming Jeng, Chiun Hsu, I-Lun Tsai, Kuan-Yu Chen, Fu-Chang Hu, Chih-Hung Hsu, Hey-Chi Hsu, Ann-Lii Cheng. Expression of FGF19/FGFR4 related biomarkers in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3131.