An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry

Sep 21, 2026

Uploaded by Jiven

N-glycans are key post-translational modifiers involved in protein folding, localization, signaling, and immune detection, yet no comparative atlas has documented N-glycome changes across diverse human tissues, especially contrasting normal versus cancer. This study applies N-glycan–targeted MALDI imaging mass spectrometry to formalin-fixed paraffin-embedded tissue microarrays containing 15 tissue types, each with matched normal and tumor cores. Spatial profiling uses MALDI-IMS workflows and glycan databases, with further structural characterization of fucosylation and sialic-acid linkages. Oligomannose, branching complexity, bisecting GlcNAc, fucosylation, and sialylation are compared, identifying cancer-associated glycan increases and decreases and supporting reference utility for future diagnostics and studies.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background and gap

Methods: MALDI-IMS on tissue microarrays

Structural profiling and comparative analysis

Findings and significance

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN An N‑glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI‑imaging mass spectrometry Elizabeth N. Wallace 1*, Connor A. West1, Colin T. McDowell 1, Xiaowei Lu1, Evelyn Bruner2, Anand S. Mehta1, Kiyoko F. Aoki‑Kinoshita3, Peggi M. Angel1 & Richard R. Drake1* N‑glycosylation is an abundant post‑translational modification of most cell‑surface proteins. N‑glycans play a crucial role in cellular functions like protein folding, protein localization, cell–cell signaling, and immune detection. As different tissue types display different N‑glycan profiles, changes in N‑glycan compositions occur in tissue‑specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N‑glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study abroad range of human tissue N‑glycomes, N‑glycan targeted MALDI imaging mass spectrometry was applied to custom formalin‑fixed paraffin‑embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in‑depth comparisons of the N‑glycome differences between tumor and normal and across tissue types. Using established MALDI‑IMS workflows and existing N‑glycan databases, the N‑glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N‑acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N‑glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI‑IMS. Determining the molecular composition of cells and tissues using “omic” technologies provides key research insights on pathway and cellular behavior in normal tissues, cancer, and other diseases. These approaches serve asa window into what is normal and what pathways, mechanisms, and interactions become dysregulated in disease states. Currently the Human Genome Project and the Human Proteome Project are two of the largest and most established of such omics programs. The Human Genome Project (https://[www.genome.gov/human-genome](www.genome.gov/human-genome)project), begun in 1988, has successfully sequenced the entire human genome assembled from the genetics of numerous volunteers, providing extremely valuable information on codes for proteins, non-coding RNA, and gene regulation, as well as leading to the emergence of proteomics1,2. This has led to the still-ongoing Human Proteome Project ([https://www.hupo.org/human-proteome-project/](https://www.hupo.org/human-proteome-project/)), which seeks to identify all the proteins coded for in human cells and biofluids, with the ability to study effects of gene knockouts or overexpression, post-translational modifications (PTMs), and protein–protein interactions3. Two large atlasing efforts for the 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. 2Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. 3Department of Bioinformatics, Soka Uni

FAQs

What gap does this study address about N-glycans and tissue types?

It addresses the lack of a comparative atlas that documents N-glycome alterations across multiple human tissue types, particularly comparisons between normal and cancerous tissues.

How were the tissue samples organized for the analysis?

The research used formalin-fixed paraffin-embedded tissue microarrays with 15 tissue types, and each array included both matched normal and tumor cores from the same pathology block selected by a pathologist.

Which molecular features were compared across tissue types to characterize cancer-associated N-glycome changes?

Comparisons included oligomannose levels, branching complexity, bisecting N-acetylglucosamine, fucosylation, and sialylation, with additional structural differentiation for fucosylation and sialic-acid linkages.

Sep 21, 2026

Uploaded by Jiven