Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma.

Abstract

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.

• Authors: Seiki Miura, Noboru Mitsuhashi, Hiroaki Shimizu, Fumio Kimura, Hiroyuki Yoshidome, Masayuki Otsuka, Atsushi Kato, Takashi Shida, Daiki Okamura, Masaru Miyazaki
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 56 (Feb 06 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 22309595 (Publication Type: Journal Article)

Chemical References

• FGF19 protein, human
• Neoplasm Proteins
• RNA, Messenger
• Fibroblast Growth Factors
• FGFR4 protein, human
• Receptor, Fibroblast Growth Factor, Type 4

Topics

• Aged
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Progression
• Female
• Fibroblast Growth Factors (genetics, metabolism, pharmacology)
• Humans
• Liver Neoplasms (metabolism, pathology)
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Neoplasm Proteins (metabolism)
• Prognosis
• RNA, Messenger (metabolism)
• Receptor, Fibroblast Growth Factor, Type 4 (metabolism)
• Survival Analysis