FBP1 Reduces ¹⁸F-FDG Uptake In Hepatocellular Carcinoma

Part 1.The relationship between FBP1 expression and the clinicopathological characteristics of HCCObjectiveTo investigate the relationship between Fructose-1,6-bisphosphatase 1（FBP1）expression and the clinicopathological characteristics of hepatocellular carcinoma（HCC）.MethodsRetrospective analysis was conducted for 75 patients with HCC.Immunohistochemistry analysis was performed to characterize the expression of FBP1 in HCC and matched noncancerous tissues.The relationship between FBP1 expression and patients’clinicopathologic characteristics were investigated.Kaplan–Meier survival analysis was employed to evaluate the prognosis of 75 HCC patients.ResultsThe expression of FBP1 in HCC was significantly lower than that in noncancerous tissues（p<0.001）.The expression of FBP1 was significantly lower in poorly differentiated HCC than in moderately differentiated and well-differentiated HCC.Kaplan–Meier survival curves demonstrated that HCC patients with low FBP1 expression presented a significantly unfavorable overall survival（OS）time（p<0.05）and disease free survival（DFS）time（p<0.05）.ConclusionFBP1 expression is a valuable prognostic biomarker for HCC and that low FBP1expression suggests unfavorable survival outcomes in HCC patients.Part 2.The relationship between ¹⁸F-FDG uptake and the expression of FBP1 in HCCObjectiveTo investigate the relationship between ¹⁸F-FDG uptake and FBP1 expression in HCC.MethodsRetrospective analysis was conducted for 85 patients with HCC who underwent¹⁸F-FDG PET/CT.The relationship between maximum standardized uptake value（SUVmax）and patients’clinicopathologic characteristics were investigated.The relationship between SUVmax and the expression of FBP1,glucose transporter 1（GLUT1）,and hexokinase 2（HK2）were also examined.ResultsSUVmax was significantly higher in primary tumors with low expression of FBP1than in primary tumors with high expression of FBP1（p<0.05）.SUVmax were significantly higher in poorly differentiated HCC than in moderately differentiated and well differentiated HCC.The expression of FBP1 was significantly lower in poorly differentiated HCC than in moderately differentiated and well-differentiated HCC.GLUT1 expression in HCC was correlated with ¹⁸F-FDG accumulation and FBP1 expression.ConclusionFBP1 expression was correlated with SUVmax,tumor differentiation,and the expression of GLUT1.Part 3.The influence of FBP1 on ¹⁸F-FDG uptake in hepatocellular carcinoma cells.ObjectiveTo investigate the effect of FBP1 on ¹⁸F-FDG uptake in hepatocellular carcinoma cells.MethodsPlasmid transfection was used to analyze the role of FBP1 in cell growth,¹⁸F-FDG uptake,lactate production in hepatocellular carcinoma cells.Hypoxia-inducible factor1 alpha（HIF1A）transcriptional activity was also investigated to evaluate the molecular mechanisms of the relationship between FBP1 expression and ¹⁸F-FDG uptake.ResultsOverexpression of FBP1 led to a significant decrease in cell proliferation（p<0.05）,¹⁸F-FDG uptake（p<0.05）,and the expression of GLUT1（p<0.05）.HIF1A transcriptional activity was decreased after FBP1 overexpression（p<0.05）.The mRNA level of GLUT1,Lactate dehydrogenase A（LDHA）and Pyruvate dehydrogenase kinase 1（PDK1）was also decreased after FBP1 overexpression（p<0.05）.When HepG2 cells were treated with CoCl₂,HIF1A transcriptional activity was significantly increased（p<0.05）.The effect of FBP1 overexpression-mediated reduced ¹⁸F-FDG uptake was reversed when HepG2 cells were treated with CoCl₂.Conclusions FBP1 may inhibit ¹⁸F-FDG uptake through the FBP1–HIF1A–GLUT1 signaling in hepatocellular carcinoma cells.Part 4.The relationship between ¹⁸F-FDG uptake and the expression of glycolytic enzymesObjectiveTo investigate the relationship between ¹⁸F-FDG uptake and the expression of LDHA,PKM2,GLUT1 and HK2 in lung adenocarcinomas.MethodsRetrospective analysis was conducted for 51 patients with lung adenocarcinomas who underwent ¹⁸F-FDG PET/CT.The relationship between SUVmax and the expression of LDHA,PKM2,GLUT1,HK2 were investigated.Then the ralationshiop between the expression of LDHA and patients’clinicopathologic characteristics were examined.The relationship between LDHA and GLUT1 expression were also assessed.ResultsSUVmax was significantly higher in primary tumors with high expression of LDHA or GLUT1 than in primary tumors with low expression of LDHA or GLUT1（p<0.05）.LDHA expression was also correlated with GLUT1 expression（p<0.05）.Kaplan–Meier survival curves demonstrated that patients with high LDHA expression presented a significantly unfavorable overall survival（OS）time（p<0.05）.ConclusionLDHA expression was correlated with SUVmax and the expression of GLUT1 in lung adenocarcinomas.High LDHA expression suggests unfavorable survival outcomes in lung adenocarcinomas.