Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the major etiology of hepatocellular cancer. Both HBV and HCV cause acute and chronic liver infections, and most chronically infected individuals remain asymptomatic for many years. About 10% to 40% of all chronic HBV carriers eventually develop hepatocellular carcinoma (HCC), and it is estimated that over one million people worldwide die because of HBV- and HCV-associated liver cancer. Indeed, HBV and HCV infections are associated with over 80% of all cases of HCC worldwide and can be as high as 96% in regions where HBV is endemic.
The glycosylation of proteins is cell specific. The N-linked glycan is a protein that reflects modifications that occurred in the cell from which it came. Sugar (glycan) structures on the same protein secreted from malignant or diseased tissue and normal cells may, and often do, differ. Our lab has observed changes in N-linked glycosylation with the development of cirrhosis and HCC and has developed a targeted glycoproteomic approach to detecting these changes. We employ a variety of proteomic techniques including two-dimensional gel electrophoresis, lectin affinity chromatography, high abundance protein depletions, ITRAQ LC/MS/MS for discovery of cancer specific biomarkers.
Selected Research Publications:
"Linkage Specific Fucosylation of Alpha-1-Antitrypsin in Liver Cirrhosis and Cancer Patients: Implications for a Biomarker of Hepatocellular Carcinoma"
Comunale MA, Rodemich-Betesh L, Hafner J, Wang M, Norton P, et al.
PLoS ONE, 5(8): e12419, 2010.
"Identification and development of fucosylated glycoproteins as biomarkers of primary hepatocellular carcinoma"
Comunale MA, Wang M, Hafner J, Krakover J, Rodemich L, Kopenhaver B, Long RE, Junaidi O, Bisceglie AM, Block TM, and AS Mehta
Journal of Proteome Research, 8(2): 595-602, 2009.
"Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma"
Wang M, Long RE, Comunale MA, Junaidi O, Marrero J, Di Bisceglie, AM, Block, TM, and AS Mehta
Cancer Epidemiology, Biomarkers & Prevention, 18(6): 1914-1921, 2009.
"Glycomic characterization of prostate-specific antigen and prostatic acid phosphatase in prostate cancer and benign disease seminal plasma fluids"
White KY, Rodemich L, Nyalwidhe JO, Comunale MA, Clements MA, Lance RS, Schellhammer PF, Mehta AS, Semmes OJ, and RR Drake
Journal of Proteome Research, 8(2): 620-630, 2009.
"N-linked glycosylation of the liver cancer biomarker GP73"
Norton PA, Comunale MA, Krakover J, Rodemich L, Pirog N, D'Amelio A, Philip R, Mehta AS, and TM Block
Journal of Cell Biochemistry, 104(1): 136-149, 2008.
"Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of hepatitis C virus-infected individuals with fibrosis and cirrhosis"
Mehta AS, Long RE, Comunale MA, Wang M, Rodemich L, Krakover J, Philip R, Marrero JA, Dwek RA, and TM Block
Journal of Virology, 82(3): 1259-1270, 2008.
"Proteomic analysis of serum associated fucosylated glycoproteins in the development of primary hepatocellular carcinoma"
Comunale MA, Krakover J, Lowman M, Long RE, Philip R, Seeholzer S, Evans AA, Hann HWL, Block TM, and AS Mehta
Journal of Proteome Research, 6(5): 308-315, 2006.
"Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans"
Block TM, Comunale MA, Romano PM, Lowman M, Fimmel C, Tennant BT, Evans A, London WT, Blumberg B, Dwek RA, Mattu TS, and A Mehta
Proceedings of the National Academy of Sciences USA, 102 (3): 779–784, 2005.
"GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma"
Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ, Comunale MA, D'Amelio A, Lok AS, and TM Block.
Journal of Hepatology, 43(6): 1007-1012, 2005.
"Comparative proteomic analysis of de-N-glycosylated serum from hepatitis B carriers reveals polypeptides that correlate with disease status"
Comunale MA, Mattu TS, Lowman M, Evans A, London WT, Dwek RA, Block TM, and A Mehta
Proteomics: 4(3): 826-838, 2004.