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Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer

Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer. Author: Cheng-Chi Wang, Chi-Huey Wong. Presenter: Bernard Shen. Introduction. Breast cancer ranks as one of the leading cancer type in the world.

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Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer

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  1. Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer Author: Cheng-Chi Wang, Chi-Huey Wong Presenter: Bernard Shen

  2. Introduction • Breast cancer ranks as one of the leading cancer type in the world. • Development of a rapid and reliable method will help decrease the mortality rate in woman • Scientists seek molecular targets of cancer cells that are absent from normal cells

  3. Globo H • A hexasaccharide and a member of cancer-associated carbohydrate antigens • Globo H expressed on the cancer cell surface, as a glycolipid and possibly as a glycoprotein. • Globo H is overexpressed on a variety of epithelial cell tumors such as lung and breast cancers, with the used of anti- Globo H monoclonal antibodies MBr1 or VK-9.

  4. Question need to further investigate associated with Globo H? • (i) Are Globo H and Gb5 differentially expressed in disease stages? • (ii) Can the glycan array be used for the quantitative and high-sensitivity detection of anti-Globo H antibody present in the serum as an indication of cancer? • (iii) Can the array be used to measure the activity of fucosyltransferase in breast cancer cells at different stages, to screen inhibitors of the enzyme and to monitor the immune response to the Globo H-based vaccine?

  5. Binding of monoclonal antibodies to Globo H and its analogues

  6. Binding curves for Globo H printed at different concentrations

  7. Glycan Microarray of Globo H • Good minic of cell surface expressing multiple glcans • very small amount of material is required • more appropriate and more sensitive system than the traditional solution-phase ELISA analysis

  8. IgG ratios of Globo H analogs to Gb5 from breast cancer patients IgM ratios of Globo H analogs to Gb5 from breast cancer patients

  9. ELISA (Enzyme-linked immunosorbent assay) • used mainly in immunology to detect the presence of an antibody in a sample • useful tool for determining serum antibody concentrations

  10. The comparison of glycanmicorarray and ELISA • The antibody levels were detectable up to 1:1,920 dilution method in Glycan microarray • 1:240 dilution in ELISA • working concentration of Globo H in array is 4 orders of magnitude lower than ELISA

  11. The comparison of sensitivity of glycan microarray and ELISA

  12. Conclusion • Quantitative analysis of the breast cancer-associated carbohydrate Globo H with minimizing the amount of serum and carbohydrate • Significant difference in anti-Globo H levels between normal and patient plasma • Demonstrate the superiority of our glycan microarray over conventional ELISA • Offer new way to analysis of fucosyltransferase activity

  13. Improvement and further direction • The number of mice (4 in the experiment ) that use to gather data for the comparison of glycan microarray and ELISA should be larger

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