ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1601368
This article is part of the Research TopicNovel Molecular Targets in Cancer TherapyView all 41 articles
Analysis of cancer-associated glycosyltransferases reveals novel targets of non-small cell lung cancer pathogenesis
Provisionally accepted
Chang Liu1,2,3,4
Thomas van Ee2,3,4
Jurriaan Janssen4,5
Ernesto Rodríguez2,3,4Yongsoo Kim4,5
Teodora Radonic5Victor W van Beusechem3,4,6
Marieke F. Fransen1,3,4
Idris Bahce1
Yvette van Kooyk2*- 1Amsterdam UMC location Vrije Universiteit Amsterdam, Pulmonary Medicine, De Boelelaan 1117, Amsterdam, Netherlands
- 2Amsterdam UMC location Vrije Universiteit Amsterdam, Molecular Cell Biology and Immunology, De Boelelaan 1117, Amsterdam, Netherlands
- 3Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, Netherlands
- 4Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, Netherlands
- 5Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pathology, De Boelelaan 1117, Amsterdam, Netherlands
- 6Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, Amsterdam, Netherlands
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Background: Aberrant glycosylation is associated with cancer progression and patient survival, of which the driving genes could act as biomarkers. Our objective was to characterize the expression of glycosylation-related genes to elucidate the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and their prospective diagnostic utility.Methods: mRNA expression data for all glyco-relevant genes was collected from 553 LUSC and 576 LUAD patients from the TCGA dataset. Differential gene expression analysis and UMAP dimension reduction analysis were used to compare mRNA expression in LUAD and LUSC.Selected genes were further confirmed through immunohistochemistry of tissue biopsies. Public single-cell RNA sequencing (scRNA-seq) data from 72 LUSC and 163 LUAD patients was retrieved to study cell type-specific expression. Galectin-7 was measured in patients' plasma by ELISA.Univariate Cox proportional regression model was used for prognostic marker detection.Results: Our analysis revealed genes differentially expressed respectively in LUSC and LUAD compared to normal lung samples. We focused on genes exhibiting high expression in LUSC (LGALS7, LGALS7B, and ST6GALNAC2) and in LUAD (LGALS4, MUC21, and ST6GALNAC1). Key glyco-related signatures were mostly observed in the malignant cell compartment. Galectin-7 concentration in plasma was upregulated in LUSC patients, but not LUAD patients. 67 genes in LUAD and 23 genes in LUSC were strongly linked to patient survival.We identified several glyco-associated biomarkers in NSCLC, including Galectin-4, Galectin-7, MUC21, ST6GALNAC1, and ST6GALNAC2. Galectin-7 is a promising clinical biomarker for detection in plasma.
Keywords: Glycosylation, Mucins, Galectins, α2,6-GalNAc-sialylation, Non-small cell lung cancer
Received: 27 Mar 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Liu, van Ee, Janssen, Rodríguez, Kim, Radonic, van Beusechem, Fransen, Bahce and van Kooyk. This is an open-access 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) or licensor 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.
* Correspondence: Yvette van Kooyk, Amsterdam UMC location Vrije Universiteit Amsterdam, Molecular Cell Biology and Immunology, De Boelelaan 1117, Amsterdam, Netherlands
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