Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma

2018 ◽  
Vol 37 (3) ◽  
pp. 214-225 ◽  
Author(s):  
Dongyang Wang ◽  
Jianjun Zhang ◽  
Zengjun Li ◽  
Jianjun Han ◽  
Yongsheng Gao ◽  
...  

Fibroblast growth factor 19 (FGF19) promotes tumor growth in various types of cancer, but its function has not been investigated in the context of colorectal adenoma. Here, we report that FGF19 expression was greater in colorectal adenoma than in normal tissues, as measured by an enzyme-linked immunosorbent assay, quantitative reverse-transcription PCR and immunohistochemistry. FGF19 expression was also elevated in a subset of human colon cancer cell lines. Moreover, FGF receptor 4 (FGFR4), the cognate receptor for FGF19, was upregulated in colorectal adenoma tissues. Lipid levels and body mass index values strongly correlated with FGF19 and FGFR4 levels in patients with colon adenomas. These observations indicate that the FGF19/FGFR4 pathway may be involved in the development of neoplasia, and that FGF19 may be a valuable diagnostic marker for the identification of patients with colorectal adenomas.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Takahiro Maeda ◽  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Kengo Kanayama ◽  
...  

Abstract Background Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA). Methods The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined. Results The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called “double negative HCC”) exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment. Conclusion Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.


2013 ◽  
Vol 304 (10) ◽  
pp. G940-G948 ◽  
Author(s):  
Justine H. Zhang ◽  
Jonathan D. Nolan ◽  
Sarah L. Kennie ◽  
Ian M. Johnston ◽  
Tracy Dew ◽  
...  

Fibroblast growth factor 19 (FGF19) is proposed to be a negative feedback regulator of hepatic bile acid (BA) synthesis. We aimed to clarify the distribution of FGF19 expression in human intestine and to investigate induction in a novel explant system. Ileal and colonic mucosal biopsies were obtained at endoscopy and analyzed for FGF19 transcript expression. Primary explants were incubated with physiological concentrations of various BA for up to 6 h, and expression of FGF19 and other genes was determined. FGF19 transcripts were detected in ileum but were unquantifiable in colon. No loss of FGF19 mRNA occurred as a consequence of the explant system. Ileal FGF19 transcript expression was induced 350-fold by 50 μM chenodeoxycholate (CDCA, n = 24, P < 0.0001) and 161-fold by 50 μM glycochenodeoxycholate (GCDCA, n = 12, P = 0.0005). The responses of other genes to CDCA or GCDCA (50 μM) were smaller: median increases of ileal bile acid binding protein, organic solute transporter-α and -β, and short heterodimer partner were 2.4- to 4.0-fold; apical membrane sodium bile acid transporter and farnesoid X receptor (FXR) showed little change. The EC50 for FGF19 transcript induction by CDCA was 20 μM. FGF19 protein concentrations were significantly higher in the culture fluid from BA-stimulated explants. FGF19 induction with cholate was 81% of that found with CDCA, but deoxycholate (40%) and lithocholate (4%) were significantly less potent. The synthetic FXR agonist obeticholic acid was much more potent than CDCA with a 70-fold FGF19 stimulation at 1 μM. We concluded that FGF19 expression in human ileum is very highly responsive to BA. Changes in FGF19 induction are a potential mechanism involved in disorders of BA homeostasis.


Tumor Biology ◽  
2013 ◽  
Vol 35 (3) ◽  
pp. 2817-2824 ◽  
Author(s):  
Abdelbaset Buhmeida ◽  
Ashraf Dallol ◽  
Adnan Merdad ◽  
Jaudah Al-Maghrabi ◽  
Mamdooh A. Gari ◽  
...  

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