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Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma
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Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma
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Journal Article
Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma
2012
Overview
Background
Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC.
Methods
We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of
FGF19
and
FGFR4
to regulate their concentrations.
Results
We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (
P
< 0.05). Univariate and multivariate analyses revealed that the tumor
FGF19
mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (
P
< 0.01,
n
= 12) and invasion (
P
< 0.01,
n
= 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (
P
< 0.01,
n
= 12). Inversely, decreasing
FGF19
and
FGFR4
expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (
P
< 0.01,
n
= 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (
P
< 0.01,
n
= 29).
Conclusions
FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cell Proliferation - drug effects
/ Female
/ Fibroblast Growth Factors - genetics
/ Fibroblast Growth Factors - metabolism
/ Fibroblast Growth Factors - pharmacology
/ Health Promotion and Disease Prevention
/ Hepatoma
/ Humans
/ Liver Neoplasms - metabolism
/ Male
/ Neoplasm Proteins - metabolism
/ Oncology
/ Proteins
/ Receptor, Fibroblast Growth Factor, Type 4 - metabolism
/ Rodents
/ Tumors
