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

*Corresponding author: Mahmoud Elalfy* and Juergen Borlak

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original research

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.

Keywords

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