Chronic active hepatitis C (HCV) remains the strongest connection to the development of hepatocellular carcinoma (HCC, liver cancer). Unfortunately, the mechanism behind hepatitis-associated cancer remains puzzling.
Such effects as oxidative stress and DNA damage are known to occur in hepatitis, through which the role of the liver in nucleic acid metabolism may be impacted.
This study evaluated the key elements in nucleic acid metabolism that might account for the biologic behavior of hepatitis-associated cancer.
Autotaxin (ENPP2) is a tumor cell motility-stimulating factor and has been linked to tumor invasion and cancer growth in several human cancers, such as breast cancer and non-small-cell lung cancer. ENPP2 has also been linked to adenosine triphosphate (ATP) and purinergenic pathways, chemical reactions occurring within a cell to maintain homeostasis. To assess the key elements in nucleic acid metabolism, researchers looked at liver tissue collected prospectively from three patient subtypes: 1) patients undergoing liver resection for non-hepatitis related diseases; 2) HCV cancer-free transplant patients; and 3) HCV patients with biopsy-confirmed HCC.
Using microarray analysis, the group sought to profile patients with respect to cancer risk. The goal of the study was to determine whether one could identify patients at high risk for the development of cancer. Differences between groups were tested by ANOVA, a statistical test that determines the significance of any given observation.
Within purine metabolism, several genes were expressed between normal liver and both HCV groups. Of these, autotaxin was significantly elevated in patients with cancer compared to HCV patients without cancer or normal liver. In addition, genes associated with autotaxin, such as the lypophosphatidic acid receptor (LPA), a potent signaling molecule, were also over-expressed in HCV patients.
“Early detection of liver cancer is crucial. For patients eligible for liver transplant, early detection is associated with excellent long term cancer survival,” said Mary Maluccio, M.D., of Indiana University in Indianapolis, Ind., and senior author of the study. “Autotaxin is one of the few genes within the purine metabolic pathway that is up-regulated in the liver of cancer patients versus their non-tumor bearing counterparts, and therefore may be a novel and important marker for early stage HCC in the hepatitis C-infected liver.”