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 #
3R01CA120206-08S2
Application #
8777752
Study Section
Program Officer
Ogunbiyi, Peter
Project Start
2014-08-01
Project End
2015-11-30
Budget Start
2014-08-01
Budget End
2014-11-30
Support Year
8
Fiscal Year
2014
Total Cost
$22,577
Indirect Cost
$8,151
Name
Drexel University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wang, Mengjun; Comunale, Mary Ann; Herrera, Harmin et al. (2016) Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection. Biochem Biophys Res Commun 476:140-5
Mehta, Anand; Comunale, Mary Ann; Rawat, Siddhartha et al. (2016) Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation. Sci Rep 6:27965
Wang, Mengjun; Devarajan, Karthik; Singal, Amit G et al. (2016) The Doylestown Algorithm: A Test to Improve the Performance of AFP in the Detection of Hepatocellular Carcinoma. Cancer Prev Res (Phila) 9:172-9
Singh, Sudhir; Pal, Kuntal; Yadav, Jessica et al. (2015) Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins. J Proteome Res 14:2594-605
Powers, Thomas W; Holst, Stephanie; Wuhrer, Manfred et al. (2015) Two-Dimensional N-Glycan Distribution Mapping of Hepatocellular Carcinoma Tissues by MALDI-Imaging Mass Spectrometry. Biomolecules 5:2554-72
Meibalan, Elamaran; Comunale, Mary Ann; Lopez, Ana M et al. (2015) Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon. Eukaryot Cell 14:371-84
Thio, Chloe L; Smeaton, Laura; Hollabaugh, Kimberly et al. (2015) Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks. AIDS 29:1173-82
Mehta, Anand; Herrera, Harmin; Block, Timothy (2015) Glycosylation and liver cancer. Adv Cancer Res 126:257-79
Zhao, Xuesen; Guo, Fang; Comunale, Mary Ann et al. (2015) Inhibition of endoplasmic reticulum-resident glucosidases impairs severe acute respiratory syndrome coronavirus and human coronavirus NL63 spike protein-mediated entry by altering the glycan processing of angiotensin I-converting enzyme 2. Antimicrob Agents Chemother 59:206-16
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

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