Is autotaxin (ENPP2) the link between hepatitis C and hepatocellular cancer?
BACKGROUND
Hepatitis C is the most significant risk factor for development of hepatocellular carcinoma. Inflammation, fibrosis, and liver cell proliferation may contribute to cancer development either through malignant hepatocyte transformation or extracellular matrix remodeling within the tumor microenvironment. The study objective was to investigate differences in gene expression between patients with Hepatitis C (+/- cancer) and normal that might explain the increased cancer risk.


METHODS
Liver tissue was collected from three patient groups: 1) healthy patients, 2) Hepatitis C patients without cancer, 3) patients with Hepatitis C and hepatocellular carcinoma. Microarray analysis was performed on samples from each group. Western blot and real-time polymerase chain reaction (PCR) analyses corroborated the microarray data. A p value of 0.05 was set as significant.


RESULTS
Microarray analysis showed overexpression of autotaxin in patients with cancer versus hepatitis patients or normal patients. Rho GTPase binding proteins (Cdc42s) associated with lysophosphatidic acid signaling were also overexpressed in cancer patients. Real-time polymerase chain reaction showed overexpression of several factors associated with autotaxin in patients with Hepatitis C (+/- cancer) versus normal patients.


CONCLUSIONS
Patients with Hepatitis C and hepatocellular carcinoma show differential expression of various components of the autotaxin pathway versus normal patients. This merits further investigation in the context of early diagnosis.
Cooper
Amanda B
AB
Department of General Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Wu
Jianmin
J
Lu
Debao
D
Maluccio
Mary A
MA
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009097:Multienzyme Complexes / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D043264:Phosphodiesterase I / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D016133:Polymerase Chain Reaction; D011755:Pyrophosphatases / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099189:Lysophospholipase D
D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D049368:Receptors, Lysophosphatidic Acid; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000099189:Lysophospholipase D