Abstract
BackgroundAlthough 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.MethodsWe 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.ResultsWe 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).ConclusionsFGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.
Highlights
Fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated
fibroblast growth factor 19 (FGF19) and FGFR4 expression in HCC We examined 40 HCC samples and corresponding noncancerous hepatic tissues for FGF19 mRNA expression using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR)
The average FGF19/GAPDH level in HCCs was significantly higher than that in noncancerous tissues. (Figure 1A; P = 0.015), whereas FGFR4 was not significantly overexpressed in HCCs compared to noncancerous tissues (Figure 1B, P = 0.055)
Summary
Fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. It has been reported that amplification or overexpression of FGFs is associated with the pathogenesis of malignant neoplasms, such as leukemias and sarcomas as well as stomach, pancreas, bladder, colon, breast, and prostate cancer [10,11,12,13,14,15]. Several correlations between overexpression, polymorphism, translocation, and truncation of FGF receptor (FGFR) and a variety of human neoplasms such as myeloma, breast, stomach, colon, bladder, and cervical cancer have been reported [16,17,18,19,20,21]. The FGF/FGFR system plays a critical role in tumor progression
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