Core-Fucosylated Tetra-Antennary N-Glycan Containing A Single N-Acetyllactosamine Branch Is Associated with Poor Survival Outcome in Breast Cancer

  • Int J Mol Sci. 2019 May 23;20(10):2528. doi: 10.3390/ijms20102528.
Harmin Herrera  1 Tinslee Dilday  2 Allison Uber  3 Danielle Scott  4 Joelle N Zambrano  5 Mengjun Wang  6 Peggi M Angel  7 Anand S Mehta  8 Richard R Drake  9 Elizabeth G Hill  10 Elizabeth S Yeh  11
Affiliations
  • 1. Graduate School of Biomedical Sciences and Professional Studies, Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, PA 19129, USA. [email protected].
  • 2. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 3. Department of Pediatrics, Division of Hematology/Oncology, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 4. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 5. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 6. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 7. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 8. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 9. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 10. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
  • 11. Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. [email protected].
Abstract

(1) Glycoproteins account for ~80% of proteins located at the cell surface and in the extracellular matrix. A growing body of evidence indicates that α-L-fucose protein modifications contribute to breast Cancer progression and metastatic disease. (2) Using a combination of techniques, including matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based in cell and on tissue imaging and glycan Sequencing using exoglycosidase analysis coupled to hydrophilic interaction ultra-high performance liquid chromatography (HILIC UPLC), we establish that a core-fucosylated tetra-antennary glycan containing a single N-acetyllactosamine (F(6)A4G4Lac1) is associated with poor clinical outcomes in breast Cancer, including lymph node metastasis, recurrent disease, and reduced survival. (3) This study is the first to identify a single N-glycan, F(6)A4G4Lac1, as having a correlation with poor clinical outcomes in breast Cancer.

Keywords
N-acetyllactosamine; N-glycan; breast cancer; core-fucose.
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