Biochemical and biophysical research communications, 2014-03, Vol.446 (1), p.54-60
2014
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- Autor(en) / Beteiligte
- Titel
- Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma
- Ist Teil von
- Biochemical and biophysical research communications, 2014-03, Vol.446 (1), p.54-60
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- •FGFR4 is significantly related with N stage in IHCC, with T stage and TNM stage in PHCC.•FGFR4 is an independent prognostic factor in IHCC and PHCC.•FGFR4 promotes proliferation, invasion and EMT in cholangiocarinoma cell lines.•Inhibitor AP24354 can decrease proliferation, invasion and induce apoptosis of CCA. Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P=0.002) and PHCC (P=0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P=0.045) and PHCC (P=0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial–mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2014.02.050Titel-ID: cdi_osti_scitechconnect_22416324
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Aged, APOPTOSIS, Apoptosis - drug effects, Bile Duct Neoplasms - drug therapy, Bile Duct Neoplasms - metabolism, Bile Duct Neoplasms - pathology, Bile Ducts, Intrahepatic, BIOLOGICAL MARKERS, Cell Line, Tumor, CELL PROLIFERATION, Cell Proliferation - drug effects, Cholangiocarcinoma, Cholangiocarcinoma - drug therapy, Cholangiocarcinoma - metabolism, Cholangiocarcinoma - pathology, CORRELATIONS, Disease Progression, Epithelial-Mesenchymal Transition, Female, Fibroblast growth factor receptor 4, FIBROBLASTS, Gene Knockdown Techniques, GROWTH FACTORS, HEK293 Cells, Hep G2 Cells, Humans, Imidazoles - pharmacology, IN VITRO, Inhibitor, Liver Neoplasms - drug therapy, Liver Neoplasms - metabolism, Liver Neoplasms - pathology, Male, Middle Aged, MULTIVARIATE ANALYSIS, Neoplasm Invasiveness, NEOPLASMS, Prognosis, Progression, Pyridazines - pharmacology, Receptor, Fibroblast Growth Factor, Type 4 - antagonists & inhibitors, Receptor, Fibroblast Growth Factor, Type 4 - genetics, Receptor, Fibroblast Growth Factor, Type 4 - metabolism, RECEPTORS, STIMULATION, Vascular Endothelial Growth Factor A - metabolism