Patient-derived organoids to study glycosylation dynamics during gastric disease

Santos-Ferreira, L.; Martins, A.M.; Duarte, H.O.; Moia, E.; Costa, A.F.; Ru, A.H. de; Faria-Ramos, I.; Matos, R.; Barros, R.; Cavadas, B.; Silva, M.; Pedrosa, S.; Batista, D.A.; Gomes, J.; Borén, T.; Sousa, F.; Casanova-Goncalves, F.; Barbosa, J.; Magalhaes, A.; Gomes, C.; Santos-Sousa, H.; Bartfeld, S.; Wuhrer, M.; Haan, N. de; Carneiro, F.; Reis, C.A.; Pinto, F.

doi:doi:10.1016/j.celrep.2025.116550

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...Show moreAberrant 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.Show less

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Patient-derived organoids to study glycosylation dynamics during gastric disease