Patient-derived organoids to study glycosylation dynamics during gastric disease

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.