Hepatocellular carcinoma (HCC) is a common primary cancer associated
frequently with hepatitis C virus (HCV). To gain insight into
the molecular mechanisms of hepatocarcinogenesis, and to identify
potential HCC markers, we performed cDNA microarray analysis on
surgical liver samples from 20 HCV-infected patients. RNA from
individual tumors was compared with RNA isolated from adjacent
nontumor tissue that was cirrhotic in all of the cases. Gene expression
changes related to cirrhosis were filtered out using experiments
in which pooled RNA from HCV-infected cirrhotic liver without
tumors was compared with pooled RNA from normal liver. Expression
of approximately 13,600 genes was analyzed using the advanced
analysis tools of the Rosetta Resolver System. This analysis revealed
a set of 50 potential HCC marker genes, which were up-regulated
in the majority of the tumors analyzed, much more widely than
common clinical markers such as cell proliferation-related genes.
This HCC marker set contained several cancer-related genes, including
serine/threonine kinase 15 (STK15), which has been implicated
in chromosome segregation abnormalities but which has not been
linked previously with liver cancer. In addition, a set of genes
encoding secreted or plasma proteins was identified, including
plasma glutamate carboxypeptidase (PGCP) and two secreted phospholipases
A2 (PLA2G13 and PLA2G7). These genes may provide potential HCC
serological markers because of their strong up-regulation in more
than half of the tumors analyzed. Thus, high throughput methods
coupled with high-order statistical analyses may result in the
development of new diagnostic tools for liver malignancies.