Defining the Human Kidney N ‐Glycome in Normal and Cancer Tissues Using MALDI Imaging Mass Spectrometry

AbstractClear ‐cell renal cell carcinoma (ccRCC) presents challenges to clinical management due to 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 an d 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 non‐tumor regions of formalin‐fixed clinical ccRCC specimens and tissue microarrays. Re gions 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 multi‐antennary N‐glycans with bisecting N‐acetylglucosami ne and multiple 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 c omposition, with specific non‐fucosylated 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...
Source: Journal of Mass Spectrometry - Category: Chemistry Authors: Tags: SPECIAL ISSUE ‐ RESEARCH ARTICLE Source Type: research