Zhong-Zhe Lin1,2,3, Chiun Hsu1,4, Yung-Ming Jeng5, Fu-Chang Hu6, Hung-Wei Pan7, Yao-Ming Wu8, Hey-Chi Hsu5, Mickey C-T Hu, Ann-Lii Cheng1,2,3,4. 1. Department of Oncology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan. 2. Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 3. National Taiwan University Cancer Center, Taipei, Taiwan. 4. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan. 5. Department of Pathology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan. 6. Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 7. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 8. Department of Surgery, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
Abstract
BACKGROUND 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.
BACKGROUND 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.
Authors: Melchiorre Cervello; Maria R Emma; Giuseppa Augello; Antonella Cusimano; Lydia Giannitrapani; Maurizio Soresi; Shaw M Akula; Stephen L Abrams; Linda S Steelman; Alessandro Gulino; Beatrice Belmonte; Giuseppe Montalto; James A McCubrey Journal: Aging (Albany NY) Date: 2020-02-04 Impact factor: 5.682