Molecular pathway analysis of glycolysis and acetate accumulation in hepatocellular carcinoma - Rationale for PET/CT imaging tracer selection

Objectives Hepatocellular carcinoma is an aggressive tumor. The appropriate treatment and prognosis depends highly on the stage. Both FDG and C-11 acetate have been used in hepatoma imaging. In this study, we systemically analyzed the metabolic gene profile changes in HCC to provide additional insight into the appropriate tracers for HCC imaging and to better link imaging to biology.

Methods A public microarray dataset including 19 normal liver tissues and 38 HCC samples was used. Transcriptome raw data were analyzed with the software Spotfire designed for microarray data analysis.

Results Three key enzymes (HK, PFK, and PKM2) in the glycolysis pathway significantly increase their expression comparing with normal liver tissue (p<0.01). The expression of UCPs and VDACs, documented candidates of Warburg effect, are up-regulated (p<0.01). In addition, the cluster of genes involved in long chain fatty acid catabolism increase their expression (p<0.01). SLC2A3 (glucose transporter), SLC16A3 and 4 (monocarboxylic acid transporters) exhibits higher expression level comparing with normal liver tissue (p<0.01).

Conclusions From the transcriptome picture, clear pathway alterations are present in many hepatomas affecting both the glycolytic and acetate pathways. Such analyses may have predictive value in hepatoma imaging tracer selection