ZHONG-ZHE LINCHIUN HSUYUNG-MING JENGHu F.-C.Pan H.-W.YAO-MING WUHsu H.-C.ANN-LII CHENG2020-02-112020-02-1120191478-3223https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068904771&doi=10.1111%2fliv.14055&partnerID=40&md5=04bca4d0b04f524f49f4cc6cb1b8226chttps://scholars.lib.ntu.edu.tw/handle/123456789/457823Background and Aims: Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signalling play critical roles in hepatocarcinogenesis. This study explored the potential of FGF19- and FGFR4-related biomarkers in predicting early tumour recurrence (ETR) and survival in patients with resectable hepatocellular carcinoma (HCC). Methods: We examined the mRNA expressions of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1) and FGF4 in 151 surgically resected, primary unifocal HCCs through quantitative real-time polymerase chain reaction. Generalized additive models were fitted to detect nonlinear effects of continuous covariates and define thresholds of biomarker expressions. Univariate and multivariate analyses were performed to evaluate prognostic values of these biomarkers for tumour recurrence and patient survival. Results: Overexpression of FGF19, FGFR4, KLB, CCND1 and FGF4 mRNA was detected in 40%, 32%, 26%, 15% and 35% of 151 tumours respectively. ETR was the strongest prognostic factor predicting worse overall survival (hazard ratio [HR], 5.678; 95% confidence interval, 3.7-8.713; P?<?0.001). Furthermore, we revealed that mRNA expression levels of KLB (HR, 3.857; P?=?0.021) and FGF19 (HR, 3.248; P?=?0.017) were significantly associated with the occurrence of ETR. Conclusions: Frequent overexpression of FGF19/FGFR4-related biomarkers was detected in resectable HCC. Expression levels of KLB and FGF19 may determine patient survival outcomes through their effects on ETR. ? 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd[SDGs]SDG3alpha fetoprotein; ccnd1 protein; cyclin D1; fibroblast growth factor 19; fibroblast growth factor 4; fibroblast growth factor receptor 4; hepatitis B surface antigen; klotho beta; messenger RNA; tumor marker; tumor protein; unclassified drug; FGF19 protein, human; FGFR4 protein, human; fibroblast growth factor; fibroblast growth factor receptor 4; KLB protein, human; membrane protein; adult; age; aged; Article; cancer prognosis; cancer recurrence; cancer staging; cancer survival; Child Pugh score; disease free survival; female; gender; gene expression; gene overexpression; human; human tissue; liver cell carcinoma; major clinical study; male; overall survival; real time polymerase chain reaction; tumor invasion; tumor volume; very elderly; young adult; carcinogenesis; cell proliferation; drug effect; genetics; liver cell carcinoma; liver tumor; metabolism; middle aged; mortality; prognosis; signal transduction; statistical model; survival analysis; Taiwan; tumor recurrence; Adult; Aged; Aged, 80 and over; Carcinogenesis; Carcinoma, Hepatocellular; Cell Proliferation; Female; Fibroblast Growth Factors; Humans; Liver Neoplasms; Logistic Models; Male; Membrane Proteins; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Receptor, Fibroblast Growth Factor, Type 4; Signal Transduction; Survival Analysis; Taiwan; Young Adultjournal article10.1111/liv.14055306989072-s2.0-85068904771