Common HCC Cell Lines Represent Only a Subgroup of Human HCC Cases

Over the past decades multiple cell lines from human hepatocellular cancer (HCC) have been generated to model HCC. However, it is not known how well these cell lines represent in vitro human HCC in vivo. For HCC, it has recently been shown by gene expression analysis that it separates at least into two genetically distinct subsets with a different course of the disease. In order to better understand these genetically defined differences, we were interested if 19 most frequently used HCC cell lines would represent these HCC subgroups. We analyzed a data of 139 genome wide microarray data from HCC samples and 19 HCC cell lines for gene expression patterns and differential pathway signalling.Using unsupervised clustering, we were able to demonstrate that the group of 19 HCC cell lines was homogenously clustering together within the one subgroup of HCC cases known for worse prognosis (group A). Accordingly, the number of genes with significantly different expression between group A and the 19 cell lines was much lower (862 genes) as compared with the group the cell lines were separated from (group B, 1488 genes). Supervised clustering using 862 genes that were significantly differently expressed between the cell lines and the HCC subgroup A clearly demonstrated the significant differences between the cell lines and subgroup B. In addition, analysis of KEGG defined signalling pathways revealed most overlapping pathways among HCC group A and the cell lines. Taking the microarray heat map into account, major differentially regulated areas demonstrated an enrichment of „Antigen processing and presentation“, „Cell adhesion molecules“, „Purine metabolism“, and „Cell cycle“ related pathways with distinct expression pattern for subgroups A and cell lines versus B. In addition, there were a few pathways exclusively activated among the cell lines, e.g. „Oxidative phosphorylation“. We conclude that modelling genetically distinct HCC subgroups in HCC cell lines may be difficult.

HCC - HCC cell lines - Hepatocellular cancer - gene expression analysis