The hypothesis of the original grant was that fucosylation increases with the development of hepatocellular carcinoma (HCC) and that fucosylated glycoprotein(s) will make sensitive and specific markers of HCC. This hypothesis has been confirmed and in our analysis of over 1000 patient samples, we have clearly shown that fucosylated glycoproteins can make sensitive and specific markers of HCC, either alone or in combination with other markers. However, in our analysis, we have determined that in addition to core fucosylation there are many other changes that occur with liver disease. Some of these changes are cancer specific and can be used to complement our existing markers, while others can occur with just liver disease (inflammation) and lead to false positives. Thus in aim 1, we will develop novel and unique reagents that will dramatically improve our assays and continue our discovery efforts to find biomarkers that can be used clinically for the management of HCC.
In aim 2 we will utilize our new lectins and continue our discovery efforts in an effort to find new biomarkers in biomarker negative populations that can complement our existing markers and lead to 100% sensitivity and 100% specificity. Finally in aim 3, we will test our lead markers in a NCI sponsored study comprising of over 350 cases of HCC and which we pre-qualified for. At the end of this 5 year period we will have validated our biomarkers and definitively proved our hypothesis that fucosylated proteins can make sensitive and specific markers of HC.

Public Health Relevance

This research project will help develop a non invasive method for the early detection of liver cancer. Liver cancer rates have doubled in the last 10 years and are continuing to rise. Unfortunately, the 5 year survival rates are only 8%, primarily due to late diagnosis. As is the case with breast cancer and cervical cancer, early detection is vital to reduce the morbidity associated with this cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA120206-06A1
Application #
8235523
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Rinaudo, Jo Ann S
Project Start
2006-04-01
Project End
2016-11-30
Budget Start
2011-12-23
Budget End
2012-11-30
Support Year
6
Fiscal Year
2012
Total Cost
$346,329
Indirect Cost
$110,964
Name
Drexel University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Powers, Thomas W; Neely, Benjamin A; Shao, Yuan et al. (2014) MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays. PLoS One 9:e106255
Thio, Chloe L; Smeaton, Laura; Saulynas, Melissa et al. (2013) Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS 27:191-201
Powers, Thomas W; Jones, E Ellen; Betesh, Lucy R et al. (2013) Matrix assisted laser desorption ionization imaging mass spectrometry workflow for spatial profiling analysis of N-linked glycan expression in tissues. Anal Chem 85:9799-806
Comunale, Mary Ann; Wang, Mengjun; Anbarasan, Nikhil et al. (2013) Total serum glycan analysis is superior to lectin-FLISA for the early detection of hepatocellular carcinoma. Proteomics Clin Appl 7:690-700
Evans, Alison A; London, W Thomas; Gish, Robert G et al. (2013) Chronic HBV infection outside treatment guidelines: is treatment needed? Antivir Ther 18:229-35
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
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
Kawamoto, Sayuri; Moriwaki, Kenta; Nakagawa, Tsutomu et al. (2011) Overexpression of ?1,6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation-independent manner. Int J Oncol 39:203-8
Romano, Patrick R; Mackay, Andrew; Vong, Minh et al. (2011) Development of recombinant Aleuria aurantia lectins with altered binding specificities to fucosylated glycans. Biochem Biophys Res Commun 414:84-9
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

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