Fibroblast growth factor 19 is correlated with an unfavorable prognosis and promotes progression by activating fibroblast growth factor receptor 4 in advanced-stage serous ovarian cancer.
Fibroblast growth factor receptor 4 (FGFR4) has been confirmed to be associated with the progression and prognosis of ovarian cancer, while the underlying mechanism has not been well elucidated and the clinical significance of its ligand, fibroblast growth factor 19 (FGF19), has not been explored. To study the clinical significance of FGF19 in advanced‑stage serous ovarian cancer, we detected the expression of FGF19 and FGFR4 by immunohistochemistry (IHC), evaluated the correlation between FGF19 and clinicopathological factors by Chi-square (χ2) test, and analyzed the association between FGF19, FGFR4 and the overall survival rate using the Kaplan‑Meier method. As a result, we demonstrated that high expression of FGF19 and FGFR4 both predicted unfavorable prognosis (P=0.033 and 0.018, respectively), whereas FGF19-FGFR4 double high expression was a more sensitive prognostic factor of advanced-stage serous ovarian cancer (P<0.001). With experiments in vitro, we demonstrated that both recombinant FGF19 and secreted FGF19 promoted ovarian cancer proliferation and invasion by activating FGFR4 and the subsequent AKT-MAPK signaling pathway, suggesting that FGF19-FGFR4 signaling may auto-activate in a paracrine or autocrine manner. In conclusion, FGF19-FGFR4 double high expression was a more sensitive prognostic factor than FGF19 or FGFR4 alone in advanced-stage serous ovarian cancer. The FGF19-FGFR4 signaling pathway can promote ovarian cancer proliferation and invasion by the AKT-MAPK signaling pathway, indicating that FGF19 could be a potential therapeutic drug target of advanced-stage serous ovarian cancer.
Department of Gynecology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Lingling
L
Hu
Department of Gynecology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China.
Lanxiang
L
Cong
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4