Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. ...Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.展开更多
BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affect...BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affecting glucose and lipid metabolism and the regulation of bile acid secretion as well as cell proliferation,differentiation,and motility.Additionally,FGF-19 secretion in an autocrine style has reportedly contributed to cancer progression in various types of malignancies including hepatocellular carcinoma(HCC).AIM To estimate the serum FGF-19 concentrations in HCC cases and assess its diagnostic performance for the detection of HCC.METHODS We recruited 90 adult participants and divided them into three equal groups:Healthy controls,cirrhosis patients,and HCC patients.Serum FGF-19 concentrations were measured using the Human FGF-19 ELISA kit.RESULTS We detected a high statistically significant difference in serum FGF-19 levels among the three groups.The highest level was observed in the HCC group,followed by the cirrhosis and control groups(236.44±40.94 vs 125.63±31.54 vs 69.60±20.90 pg/mL,respectively,P≤0.001).FGF-19 was positively correlated with alpha fetoprotein(AFP;r=0.383,P=0.003)and international normalised ratio(r=0.357,P=0.005),while it was negatively correlated with albumin(r=-0.500,P≤0.001).For the detection of HCC,receiver operating characteristic curve analysis showed that the best cut-off point of AFP was>8.2 ng/mL with an area under the curve(AUC)of 0.78,sensitivity of 63.33%,specificity of 83.33%,positive predictive value(PPV)of 79.2%,negative predictive value(NPV)of 69.4%,and total accuracy of 78%.However,FGF-19 at a cut-off point>180 pg/mL had an AUC of 0.98,sensitivity of 100%,specificity of 90.0%,PPV of 90.0%,NPV of 100%,and total accuracy of 98%.CONCLUSION FGF-19 represents a possible novel non-invasive marker for HCC.It may improve the prognosis of HCC patients due to its utility in several aspects of HCC detection and management.展开更多
Background and Aims:Fibroblast growth factor(FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma.Whether it plays a role in the development or course of human cholangiocarcinoma remains t...Background and Aims:Fibroblast growth factor(FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma.Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined.The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.Methods:Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19(0-50 ng/mL)for 6 weeks,followed by 6 weeks with medium alone.Cell proliferation,invasion,stem cell surface markers,oncofetoprotein expression,state of differentiation,epithelial-mesenchymal transition(EMT)and interleukin(IL)-6 expression were documented at various time intervals throughout the 12-week period.Results:FGF19 exposure was associated with significant increases in cell proliferation,de-differentiation,EMT and IL-6 expression.However,each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period.The remaining cell properties remained unaltered.Conclusions:Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant,human cholangiocytes.展开更多
基金supported by the Major Program of the Shanghai Municipality for Basic Research(10JC1412400)the National Natural Science Foundation Major International(Regional)Joint Research Project(81220108006)
文摘Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight.
文摘BACKGROUND Fibroblast growth factor 19(FGF-19)is one of the founding members of the endocrine FGF subfamily.Recently,it has been the subject of much interest owing to its role in various physiological processes affecting glucose and lipid metabolism and the regulation of bile acid secretion as well as cell proliferation,differentiation,and motility.Additionally,FGF-19 secretion in an autocrine style has reportedly contributed to cancer progression in various types of malignancies including hepatocellular carcinoma(HCC).AIM To estimate the serum FGF-19 concentrations in HCC cases and assess its diagnostic performance for the detection of HCC.METHODS We recruited 90 adult participants and divided them into three equal groups:Healthy controls,cirrhosis patients,and HCC patients.Serum FGF-19 concentrations were measured using the Human FGF-19 ELISA kit.RESULTS We detected a high statistically significant difference in serum FGF-19 levels among the three groups.The highest level was observed in the HCC group,followed by the cirrhosis and control groups(236.44±40.94 vs 125.63±31.54 vs 69.60±20.90 pg/mL,respectively,P≤0.001).FGF-19 was positively correlated with alpha fetoprotein(AFP;r=0.383,P=0.003)and international normalised ratio(r=0.357,P=0.005),while it was negatively correlated with albumin(r=-0.500,P≤0.001).For the detection of HCC,receiver operating characteristic curve analysis showed that the best cut-off point of AFP was>8.2 ng/mL with an area under the curve(AUC)of 0.78,sensitivity of 63.33%,specificity of 83.33%,positive predictive value(PPV)of 79.2%,negative predictive value(NPV)of 69.4%,and total accuracy of 78%.However,FGF-19 at a cut-off point>180 pg/mL had an AUC of 0.98,sensitivity of 100%,specificity of 90.0%,PPV of 90.0%,NPV of 100%,and total accuracy of 98%.CONCLUSION FGF-19 represents a possible novel non-invasive marker for HCC.It may improve the prognosis of HCC patients due to its utility in several aspects of HCC detection and management.
文摘Background and Aims:Fibroblast growth factor(FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma.Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined.The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.Methods:Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19(0-50 ng/mL)for 6 weeks,followed by 6 weeks with medium alone.Cell proliferation,invasion,stem cell surface markers,oncofetoprotein expression,state of differentiation,epithelial-mesenchymal transition(EMT)and interleukin(IL)-6 expression were documented at various time intervals throughout the 12-week period.Results:FGF19 exposure was associated with significant increases in cell proliferation,de-differentiation,EMT and IL-6 expression.However,each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period.The remaining cell properties remained unaltered.Conclusions:Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant,human cholangiocytes.