BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer related mortality worldwide,with poor survival due to late diagnosis.Currently,biomarkers have limited use in early diagnosis of PC.Macrophage inhibitory cy...BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer related mortality worldwide,with poor survival due to late diagnosis.Currently,biomarkers have limited use in early diagnosis of PC.Macrophage inhibitory cytokine-1 or growth differentiation factor-15(MIC-1/GDF15)has been implicated as a potential serum biomarker in PC and other malignancies.AIM To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program.METHODS A feasibility prospective single centre cohort study was performed.Participants recruited for yearly surveillance with endoscopic ultrasound(EUS)had serial fasting blood samples collected before EUS for MIC-1/GDF15,C-reactive protein and carbohydrate antigen 19-9.Patients were stratified into five groups based on EUS findings:Normal;pancreatic cysts,branch-duct intraductal papillary mucinous neoplasm;diffuse non-specific abnormalities;and neoplastic tumours.MIC-1/GDF15 serum levels were quantified using ELISA.Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging(MRI)or computed tomography.RESULTS One hundred twenty participants were prospectively recruited from 2011-2018.Forty-seven participants(39.2%)had an abnormal EUS and five participants(4.2%)were diagnosed with neoplastic tumours,three by EUS(two pancreatic and one liver)and two by MRI/computed tomography(breast cancer,bladder cancer),which were performed for follow up of abnormal EUS.Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis[area under curve(AUC)=0.814,P=0.023].Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm(AUC=0.644)and neoplastic tumours noted on EUS(AUC=0.793),however this was not significant(P=0.188 and 0.081 respectively).Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS(P=0.213).Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours(Median=1039.6,interquartile range=727.0-1977.7)compared to those diagnosed with a benign lesion(Median=570.1,interquartile range=460.7-865.2)on EUS and MRI(P=0.012).CONCLUSION In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC.Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15.Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.展开更多
Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future is...Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.展开更多
BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is i...BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.展开更多
BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It ha...BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection.METHODS PubMed,Reference Citation Analysis,CNKI,and Goggle Scholar were explored by using related MeSH keywords and data such as the first author’s name,study duration,type and place of study,sample size and subgroups of participants if any,serum/plasma GDF-15 level in pg/mL,area under the curve and cut-off value in receiver operating characteristic analysis,method of measurement of GDF-15,and the main conclusion were extracted.RESULTS In all studies,the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients,and it was significantly associated with severity,hypoxemia,viral load,and worse clinical consequences.In addition,GDF-15 levels were correlated with C-reactive protein,D-dimer,ferritin and procalcitonin,and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection.Hence,GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2.CONCLUSION Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.展开更多
BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are ...BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.展开更多
基金Pancare Foundation for their ongoing support and providing funding for the coordinator positionGarvan Institute of Medical Research for their support and ongoing collaboration.
文摘BACKGROUND Pancreatic cancer(PC)is a leading cause of cancer related mortality worldwide,with poor survival due to late diagnosis.Currently,biomarkers have limited use in early diagnosis of PC.Macrophage inhibitory cytokine-1 or growth differentiation factor-15(MIC-1/GDF15)has been implicated as a potential serum biomarker in PC and other malignancies.AIM To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program.METHODS A feasibility prospective single centre cohort study was performed.Participants recruited for yearly surveillance with endoscopic ultrasound(EUS)had serial fasting blood samples collected before EUS for MIC-1/GDF15,C-reactive protein and carbohydrate antigen 19-9.Patients were stratified into five groups based on EUS findings:Normal;pancreatic cysts,branch-duct intraductal papillary mucinous neoplasm;diffuse non-specific abnormalities;and neoplastic tumours.MIC-1/GDF15 serum levels were quantified using ELISA.Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging(MRI)or computed tomography.RESULTS One hundred twenty participants were prospectively recruited from 2011-2018.Forty-seven participants(39.2%)had an abnormal EUS and five participants(4.2%)were diagnosed with neoplastic tumours,three by EUS(two pancreatic and one liver)and two by MRI/computed tomography(breast cancer,bladder cancer),which were performed for follow up of abnormal EUS.Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis[area under curve(AUC)=0.814,P=0.023].Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm(AUC=0.644)and neoplastic tumours noted on EUS(AUC=0.793),however this was not significant(P=0.188 and 0.081 respectively).Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS(P=0.213).Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours(Median=1039.6,interquartile range=727.0-1977.7)compared to those diagnosed with a benign lesion(Median=570.1,interquartile range=460.7-865.2)on EUS and MRI(P=0.012).CONCLUSION In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC.Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15.Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.
基金All authors have no conflict of interest regarding this paper. This work was supported by Grant National Natural Science Foundation of China （81400262） ＆ Backbone Fund of Peking University Third Hospital.
基金supported by the Beijing Municipal Science and Technology Committee(D0906006000091)the Ministry of Science and Technology of the People’s Republic of China,State Science and Technology Support Program(No.2011BAI11B05).
文摘Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.
基金Supported by National Natural Science Foundation of China,No.81771373Key Research and Development Plan of Zibo City,No.2019ZC010169 and No.2019ZC010166.
文摘BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.
文摘BACKGROUND Growth differentiation factor(GDF)-15 is a member of a transforming growth factor-βcytokine superfamily that regulates metabolism and is released in response to inflammation,hypoxia and tissue injury.It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions,such as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection.METHODS PubMed,Reference Citation Analysis,CNKI,and Goggle Scholar were explored by using related MeSH keywords and data such as the first author’s name,study duration,type and place of study,sample size and subgroups of participants if any,serum/plasma GDF-15 level in pg/mL,area under the curve and cut-off value in receiver operating characteristic analysis,method of measurement of GDF-15,and the main conclusion were extracted.RESULTS In all studies,the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients,and it was significantly associated with severity,hypoxemia,viral load,and worse clinical consequences.In addition,GDF-15 levels were correlated with C-reactive protein,D-dimer,ferritin and procalcitonin,and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection.Hence,GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2.CONCLUSION Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.
基金the National Natural Science Foundation of China, No. 81600617
文摘BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.
