Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry

Research output: Contribution to journalArticle

Authors

  • Richard R. Drake
  • Colin McDowell
  • Connor West
  • Fred David
  • Thomas W. Powers
  • Tamara Nowling
  • Evelyn Bruner
  • Anand S. Mehta
  • Peggi M. Angel
  • Laura A. Marlow
  • Han W. Tun
  • John A. Copland

External Institution(s)

  • Medical University of South Carolina
  • Mayo Clinic Jacksonville, FL

Details

Original languageEnglish (US)
Article numbere4490
JournalJournal of Mass Spectrometry
Volume55
Issue number4
StatusPublished - Apr 1 2020
Peer-reviewedYes

Abstract

Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence. Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined. Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays. Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features. Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues. These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation. A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions. Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes. The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues. These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.

    Research areas

  • MALDI imaging, N-glycosylation, clear-cell renal cell carcinoma, fucosylation, polycystic kidney disease

Citation formats

APA

Drake, R. R., McDowell, C., West, C., David, F., Powers, T. W., Nowling, T., ... Copland, J. A. (2020). Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry. Journal of Mass Spectrometry, 55(4), [e4490]. https://doi.org/10.1002/jms.4490

Harvard

Drake, RR, McDowell, C, West, C, David, F, Powers, TW, Nowling, T, Bruner, E, Mehta, AS, Angel, PM, Marlow, LA, Tun, HW & Copland, JA 2020, 'Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry', Journal of Mass Spectrometry, vol. 55, no. 4, e4490. https://doi.org/10.1002/jms.4490