This is a proposal to continue the Early Detection of Liver Cancer Biomarker Discovery Laboratory of the EDRN. Our over-all goal has been to identify and develop biomarkers for the early detection of liver cancer. Our hypothesis, tested within the first period of support, that changes in the amount or modification of serum polypeptides correlate with the onset of hepatocellular carcinoma (HCC) or hepatitis, has been confirmed. We will build upon our exciting initial proteomic studies of cell lines and human serum derived from those at risk for liver cancer in which several promising approaches and biomarker leads were found. For example, we will determine the possibility that GP73, a resident Golgi protein whose level in the circulation was found by us to correlate with a diagnosis of liver cancer, can be used as a biomarker of disease. Pilot studies, in cooperation with NCI consortia, showed that GP73 levels were among the best biomarkers of liver disease to be tested. Moreover, different glycoforms appeared to be associated with tissue and secreted states and may in themselves vary with clinical status. Therefore, the GP73 detection assay, developed by us, will be refined to exploit our new insights to improve specificity, and made robust for larger validation studies to determine true sensitivity, specificity and selectivity, in people. In addition, new biomarkers discovered by our proteomic and glycobiology research will be contributed to the pipeline. The possibility that promising biomarker levels are influenced by antiviral therapy will also be determined. The most promising candidates, chosen on the basis of selectivity and sensitivity criteria, will be advanced to the validation stage for ultimate utility determination.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA084951-10S4
Application #
8116743
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Wagner, Paul D
Project Start
1999-09-30
Project End
2011-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
10
Fiscal Year
2010
Total Cost
$154,000
Indirect Cost
Name
Drexel University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lamontagne, Anne; Long, Ronald E; Comunale, Mary Ann et al. (2013) Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection. PLoS One 8:e64992
Nie, Hui; Evans, Alison A; London, W Thomas et al. (2012) Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion. J Hepatol 56:795-802
Comunale, Mary Ann; Wang, Mengjun; Rodemich-Betesh, Lucy et al. (2011) Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 20:1222-9
Nie, Hui; Evans, Alison A; London, W Thomas et al. (2011) Quantification of complex precore mutations of hepatitis B virus by SimpleProbe real time PCR and dual melting analysis. J Clin Virol 51:234-40
Liu, Yuanjie; Testa, James S; Philip, Ramila et al. (2011) A ubiquitin independent degradation pathway utilized by a hepatitis B virus envelope protein to limit antigen presentation. PLoS One 6:e24477
Hann, Hie-Won; Wang, Mengjun; Hafner, Julie et al. (2010) Analysis of GP73 in patients with HCC as a function of anti-cancer treatment. Cancer Biomark 7:269-73
Comunale, Mary Ann; Rodemich-Betesh, Lucy; Hafner, Julie et al. (2010) Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma. PLoS One 5:e12419
Comunale, Mary Ann; Wang, Mengjun; Hafner, Julie et al. (2009) Identification and development of fucosylated glycoproteins as biomarkers of primary hepatocellular carcinoma. J Proteome Res 8:595-602
Wang, Mengjun; Long, Ronald E; Comunale, Mary Ann et al. (2009) Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 18:1914-21
Norton, Pamela A; Comunale, Mary Ann; Krakover, Jonathan et al. (2008) N-linked glycosylation of the liver cancer biomarker GP73. J Cell Biochem 104:136-49

Showing the most recent 10 out of 16 publications