Klotho-beta and fibroblast growth factor 19 expression correlates with early recurrence of resectable hepatocellular carcinoma
- PMID: 30698907
- DOI: 10.1111/liv.14055
Klotho-beta and fibroblast growth factor 19 expression correlates with early recurrence of resectable hepatocellular carcinoma
Erratum in
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CORRIGENDUM.Liver Int. 2020 Sep;40(9):2309. doi: 10.1111/liv.14619. Liver Int. 2020. PMID: 32930520 No abstract available.
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.
Keywords: FGF19; FGFR4; KLB; hepatocellular carcinoma.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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References
REFERENCES
-
- El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology. 2014;60:1767-1775.
-
- Lin ZZ, Hsu HC, Hsu CH, et al. The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma. J Hepatol. 2009;50:518-527.
-
- Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48:S20-S37.
-
- Lin ZZ, Jeng YM, Hu FC, et al. Significance of Aurora B overexpression in hepatocellular carcinoma. BMC Cancer. 2010;10:461.
-
- Désert R, Rohart F, Canal F, et al. Human hepatocellular carcinomas with a periportal phenotype have the lowest potential for early recurrence after curative resection. Hepatology. 2017;66:1502-1518.
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