Patient-derived organoids to study glycosylation dynamics during gastric disease

Researchers from the Glycobiology in Cancer at i3S established a unique biobank of patient-derived gastric organoids showing that these models faithfully reproduce human tissue glycosylation across stages of gastric carcinogenesis. The study further demonstrates that organoids retain tumor heterogeneity and dynamically regulate Lewis antigens, shaping Helicobacter pylori interactions.

Authors and Affiliations:

Liliana Santos-Ferreira^1,2,3, Álvaro M. Martins^1,2,3, Henrique O. Duarte^1,2, Eva Moia^1,2, Ana F. Costa^1,2,3, Arnoud H. de Ru^4,  Isabel Faria-Ramos^1,2, Rita Matos^1,2, Rita Barros^1,2,5,6, Bruno Cavadas^1, Marta Silva^1, Sofia Pedrosa^6, Diana A. Batista^6, Joana Gomes^1,2 ∙ Thomas Borén^7, Fabiana Sousa^8,9, Frederica Casanova-Gonçalves^8,9, José Barbosa^8,9, Ana Magalhães^1,2,3, Catarina Gomes^1,2, Hugo Santos-Sousa^1,5,8,10, Sina Bartfeld^11,12, Manfred Wuhrer^4, Noortje de Haan^4, Fátima Carneiro^1,2,13,14, Celso A. Reis^1,2,3,5, Filipe Pinto^1,2,15,16

1. i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2. IPATIMUP – Institute of Molecular Pathology and Immunology, University of Porto, Portugal
3. Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Portugal
4. Center for Proteomics and Metabolomics, Leiden University Medical Center, Netherlands
5. Faculty of Medicine, University of Porto (FMUP), Portugal
6. Serviço de Anatomia Patológica, Unidade Local de Saúde (ULS) de São João, Portugal
7. Department of Medical Biochemistry and Biophysics, Umeå University, Sweden
8. Serviço de Cirurgia, ULS de São João, Portugal
9. RISE-Health, Department of Surgery and Physiology, FMUP, Portugal
10. Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, Portugal
11. Simulierte Mensch, Technische Universität Berlin & Charité – Universitätsmedizin Berlin, Germany
12. Institute of Biotechnology, Technische Universität Berlin, Germany
13. Department of Pathology, FMUP, Portugal
14. Department of Pathology, ULS de São João, Portugal
15. Present address: i3S, Universidade do Porto, Portugal
16. Lead Contact: Filipe Pinto ([email protected])

Abstract:

Aberrant cellular glycosylation is a key event that accompanies and actively sustains gastric neoplastic transformation. Patient-derived organoids (PDOs) have recently emerged as promising ex vivo models to study human gastric diseases; however, their glycosylation landscape remains unknown. To evaluate gastric PDOs as avatars of in vivo tissue glycosylation, a biobank of gastric PDOs (n = 56) was generated from gastric mucosa samples of non-tumoral obese patients (n = 11), adjacent tumor mucosa (n = 26), and gastric tumor tissue (n = 19). PDOs reproduce distinct stages of gastric carcinogenesis and recapitulate the gastric tissue-associated glycosylation profiles. PDOs capture glycan inter- and intra-tumoral heterogeneity, which is maintained over time and upon biobanking and xenografting. Furthermore, expression of type I/II Lewis antigens is dynamically controlled by the PDO’s differentiation status, influencing Helicobacter pylori binding, mirroring the gastric epithelium-tissue interactions. This study establishes PDOs as robust ex vivo tools to study gastric glycan dynamics in both gastric physiological and pathological settings.

Journal: Cell Reports (2025)

Link: https://doi.org/10.1016/j.celrep.2025.116550