This research grant will attempt to identify all the serum glycoproteins that have increased levels of fucosylation in the sera of patients with hepatocellular carcinoma (HCC). It is acknowledged in the literature that changes in glycosylation occur with cancer. More importantly we have shown that there is an increase in the level of core fucosylation associated with the development of liver cancer. However, the proteins on which these changes occur are, for the most part, unknown. Hence, we propose to evaluate serum, in both a pre-cancerous and cancerous state, for alterations in the amount of fucosylation associated with all serum glycoproteins. This comparative study will use a technology that will exploit a variety of fucose recognizing lectins to extract specific glycoproteins and identify them using LC MS/MS based proteomic methodologies. Glycoproteins that alter with the development of cancer will be evaluated further for their potential as biomarkers of virally induced liver cancer. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA120206-01A1
Application #
7198314
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Wagner, Paul D
Project Start
2006-09-26
Project End
2011-07-31
Budget Start
2006-09-26
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$395,184
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
West, Connor A; Wang, Mengjun; Herrera, Harmin et al. (2018) N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue As Determined through in Situ Glycan Imaging. J Proteome Res 17:3454-3462
Mehta, Anand S; Lau, Daryl T-Y; Wang, Mengjun et al. (2018) Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma. PLoS One 13:e0203149
Black, Alyson P; Mehta, Anand S (2018) The search for biomarkers of hepatocellular carcinoma and the impact on patient outcome. Curr Opin Pharmacol 41:74-78
Wang, Mengjun; Shen, Jiabin; Herrera, Harmin et al. (2018) Biomarker analysis of fucosylated kininogen through depletion of lectin reactive heterophilic antibodies in hepatocellular carcinoma. J Immunol Methods 462:59-64
Kaczor-Urbanowicz, Karolina El?bieta; Deutsch, Omer; Zaks, Batia et al. (2017) Identification of salivary protein biomarkers for orthodontically induced inflammatory root resorption. Proteomics Clin Appl 11:
Betesh, Lucy; Comunale, Mary Ann; Wang, Mengjun et al. (2017) Identification of fucosylated Fetuin-A as a potential biomarker for cholangiocarcinoma. Proteomics Clin Appl 11:
Wang, Mengjun; Sanda, Miloslav; Comunale, Mary Ann et al. (2017) Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC. Cancer Epidemiol Biomarkers Prev 26:795-803
Holst, Stephanie; Heijs, Bram; de Haan, Noortje et al. (2016) Linkage-Specific in Situ Sialic Acid Derivatization for N-Glycan Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded Tissues. Anal Chem 88:5904-13
Heijs, Bram; Holst, Stephanie; Briaire-de Bruijn, Inge H et al. (2016) Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section. Anal Chem 88:7745-53
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

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