Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression

Sep 21, 2026

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Colorectal cancer (CRC) remains a leading cause of cancer death, with progression from adenomas to adenocarcinomas often occurring silently for 10–15 years due to limited detection at pre-invasive stages. The tumor microenvironment, including immune cells, critically shapes initiation, growth, and metastasis. To clarify this immune–tumor relationship, N-glycomic profiling was performed using MALDI-MSI, identifying nearly 100 N-glycan species and revealing stage-dependent shifts from normal to cancer tissue, including changes in high-mannose and paucimannose patterns. Distinct CD20+ B-cell and CD3/CD44+ T-cell immune clusters showed predictive N-glycan signature profiles.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

Background on colorectal cancer and immune microenvironment

N-glycomic profiling approach

MALDI-MSI for immune and tissue characterization

TYPE Original Research PUBLISHED 11 January 2024 DOI 10.3389/fphar.2023.1337319 OPEN ACCESS EDITED BY Lucas Duarte Nicolau, Federal University of the Parnaíba Delta, Brazil REVIEWED BY Teodora Alexa-Stratulat, Grigore T. Popa University of Medicine and Pharmacy, Romania Salomé S. Pinho, University of Porto, Portugal *CORRESPONDENCE Richard R. Drake, [draker@musc.edu](draker@musc.edu) RECEIVED 12 November 2023 ACCEPTED 26 December 2023 PUBLISHED 11 January 2024 CITATION Young LEA, Nietert PJ, Stubler R, Kittrell CG, Grimsley G, Lewin DN, Mehta AS, Hajar C, Wang K, O’Quinn EC, Angel PM, Wallace K and Drake RR (2024), Utilizing multimodal mass spectrometry imaging for proﬁling immune cell composition and N-glycosylation across colorectal carcinoma disease progression. Front. Pharmacol. 14:1337319 . doi: 10.3389/fphar.2023.1337319 COPYRIGHT © 2024 Young, Nietert, Stubler, Kittrell, Grimsley, Lewin, Mehta, Hajar, Wang, O’Quinn, Angel, Wallace and Drake. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Utilizing multimodal mass spectrometry imaging for proﬁling immune cell composition and N-glycosylation across colorectal carcinoma disease progression Lyndsay E. A. Young 1,2, Paul J. Nietert 3, Rachel Stubler 4, Caroline G. Kittrell 1, Grace Grimsley 1, David N. Lewin 5, Anand S. Mehta 1,2, Chadi Hajar 5, Katherine Wang 5, Elizabeth C. O’Quinn 2,5, Peggi M. Angel 1,2, Kristin Wallace 2,3 and Richard R. Drake 1,2* 1Department of Cell and Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Medical University of South Carolina, Charleston, SC, United States, 2Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States, 3Translational Science Laboratory, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States, 4Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, United States, 5Department of Regenerative Medicine and Cell Biology, College of Medicine, Medical University of South Carolina, Charleston, SC, United States, 6Department of Pathology and Laboratory Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, United States Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from speciﬁc genetic mutations, progressing from pre-cancerous adenomas toadenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identiﬁed at pre-invasive stages, allowing progression to occur silently over 10–15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic proﬁling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI) . We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome proﬁles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in paucimannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratiﬁcation in the N-glycome proﬁle was observed between non-mucinousand mucinous CRC tissues, driven by pauci-man

FAQs

What clinical challenge does the study address in colorectal cancer?

CRC often progresses from pre-cancerous stages to adenocarcinomas over 10–15 years and only a fraction is detected before invasion, limiting early intervention. The work targets improved biomarkers through profiling immune-related glycosylation changes.

How was N-glycosylation measured across disease progression?

The study used matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI) to perform N-glycomic profiling across samples. It detected nearly 100 N-glycan species and assessed shifts with progression.

Which immune cell clusters showed distinctive predictive N-glycan signatures?

Immune clusters of CD20+ B cells and CD3/CD44+ T cells exhibited distinctive, predictive signature profiles. These signatures were linked to specific N-glycan features such as bisecting and branched glycans.

Sep 21, 2026

Uploaded by Jiven