Researchers have identified multiple changes in the gene-expression patterns of cells involved with tumor progression in liver cancer patients

Virginia Commonwealth University researchers have identified multiple changes in the gene-expression patterns of cells involved with tumor progression in liver cancer patients and in those with cirrhosis, which may help scientists predict a person’s risk of developing primary liver cancer.

About 3 million Americans are chronically infected with hepatitis C virus, HCV, which causes inflammation of the liver. It is the leading cause of liver transplantation in the United States, and is the main cause of cirrhosis, which typically leads to primary liver cancer or hepatocellular carcinoma, HCC.

Primary liver cancer is the fifth most common cancer and the third leading cause of cancer deaths in the world. Treatment options for primary liver cancer include chemotherapy, chemoembolization, ablation and proton-beam therapy. Liver transplantation offers the best chance for a cure in patients with small tumors and significant associated liver disease.

In a study published in the May 2004 issue of the journal Liver Transplantation, VCU School of Medicine researchers reported consistent differences between the gene-expression patterns in primary liver cancer due to HCV infection — HCV-HCC — and those of early HCV-cirrhosis, late HCV cirrhosis and normal control livers. They also observed consistent differences in the gene-expression patterns of the different stages of cirrhosis and the different stages of the cancer. These findings indicate the possibility for identifying prognostic factors associated with tumor progression in HCC.

“If we can detect particular gene and protein expressions that are leading to a potentially lethal disease, then we may be able to intervene before that potentially lethal disease becomes incurable, or eliminate those components before a patient becomes infected,” said lead investigator, Robert A. Fisher, M.D., director of the liver transplant program at the VCU Medical Center, and a professor of surgery.

Fisher and his colleagues analyzed gene expression of different stages of liver disease ranging from early cirrhosis to severely advanced cirrhosis, with and without HCC, in HCV-infected patients at the time of liver transplantation. They used DNA microarray technology to study the gene-expression profile and gene activation of thousands of genes and sequences in samples taken from diseased liver tissue. In previous studies, DNA microarrays have been used to outline changes in gene expression in liver samples obtained from patients with HCC and have allowed for the identification of gene sets that may be useful as potential microarray-based diagnostic tools.

Researchers found that the genes responsible for tumor suppression and regulation of the cell cycle were underexpressed in the early-and-late HCV cirrhosis samples. This finding suggests that different molecular mechanisms related to cancer progression would be activated. They also found that there were multiple molecular alterations during the HCV-HCC tumor progression.

“If these findings are applied to a larger group of patients with HCV and/or HCC, and the gene sequences and characteristics repeat themselves over and over, we may be able to identify what gene patterns may start to change, or become altered, before the clinical disease develops. We may be able to intervene before the patient is at greater risk — perhaps before the clinical disease is detected,” Fisher said.

“Eventually, we may be able to predict that the clinical disease will appear within a certain time period, a certain number of years,” Fisher said. “If our prediction is correct, then we can propose that this technique be used for preventative diagnosis.”