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Metabolically, ccRCC has a well\u2010described 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\u2010glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin\u2010fixed clinical ccRCC specimens and tissue microarrays. Regions of normal kidney tissue samples were also evaluated for N\u2010linked glycan\u2010based distinctions between cortex, medullar, glomeruli, and proximal tubule features. Most notable was the proximal tubule localized detection of abundant multiantennary N\u2010glycans with bisecting N\u2010acetylglucosamine and multziple fucose residues. These glycans are absent in ccRCC tissues, while multiple tumor\u2010specific N\u2010glycans were detected with tri\u2010 and tetra\u2010antennary structures and varying levels of fucosylation and sialylation. A polycystic kidney disease tissue was also characterized for N\u2010glycan 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\u2010glycan 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.<\/jats:p>","DOI":"10.1002\/jms.4490","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T15:50:30Z","timestamp":1576857030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Defining the human kidney N\u2010glycome in normal and cancer tissues using MALDI imaging mass spectrometry"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6285-6440","authenticated-orcid":false,"given":"Richard R.","family":"Drake","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Pharmacology and Experimental Therapeutics Medical University of South Carolina  Charleston SC 29425 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