Correlation of 18F-Fluorodeoxyglucose Glucose Uptake by Liver Cancer and Transcriptional Regulation of the Warburg Effects in ATT-MYC Mouse Model of Liver Cancer

Authors

  • Mahmoud Elalfy, PhD Author
  • Juergen Borlak, MD Author

Keywords:

FFluorodeoxyglucose (FDG), MicroPET, Exon array expression, Hepatocellular carcinoma (HCC), Att-myc transgenic mice, Diethylnitrosamine (DEN), Butylated hydroxytoluene (BHT), Glucose metabolism.

Abstract

Background
It was previously reported that diethylnitrosamine (DEN) enhanced liver cancer progression in ATT-MYC mouse model of liver 
cancer. Radiogenomics is a new tool in advanced science technology that gives information on tumor biology, non-tumor surrounding tissue, the degree of tumor size and presence of necrosis of cells especially with joined micro computed tomography 
– positron emission tomographys (CT/PETs).
Aim
To evaluate the correlation of gene expression and non-invasive microPET information of the liver tumors at different points of 
the stage of growth.
Methods
Exon array expression of the liver of ATT-MYC mice treated with DEN or butylated hydroxytoluene (BHT) compared to control 
non-transgenic mice were analyzed by array track and the current data were also compared to microarray expression of liver tumor 
of ATT-MYC mice.
Results
The expression of genes responsible for glucose transport such as glut1, 3, 4, hk1, slc1a5, slc1a1, slc1a4, slc1a2, gp6c and gpc-1-3-4
were up-regulated significantly in DEN-treated transgenic mice immediately after end of treatment (p≤0.05), while glut2 (fold 
change 0.9503, p-value 0.4385) and hk2 (fold change 3.0589, p-value 0.0565) genes were increased not significantly immediately 
after end of treatment. Additionally, at 4.5-months of observation after the end of treatment slc1a5, slc38a2, glut1, glut4 and gpc3-4
genes had a significant fold change in liver tumor tissue in DEN treated mice when compared to BHT or control transgenic or 
non-transgenic one. While hk1, 2, slc5a1, slc1a4, glut2, glut3, g6pc and gpc-1 genes were increased non-significantly in the liver of 
treated mice when compared to control group at 4.5-months of observation after the end of treatment. Notably, c-myc, hif-1 and 
aldoa glycolytic genes were expressed significantly both time points of 4 and 8.5-months while ldhb, hk-2 and PKM2 were increased 
non-significantly in DEN treatment when compared to BHT/control non-transgenic animals.
Conclusion
There is a definitive correlation between genes responsible for glucose transport and 18F-Fluorodeoxyglucose (FDG) uptake in the 
early and advanced degree of liver carcinogenesis. This study of glucose pathway in Hepatocellular carcinoma (HCC) at different 
stages of early and advanced one is the potential for therapeutic anticancer therapy. 

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Published

2020-05-16