Tumorigenicity and prediction of clinical prognosis of patient‐derived gastric cancer organoids

Abstract

Dear Editor,In this study, we established a biobank of gastric tumour organoids (GTOs), which retained primary tumour characteristics. The response of GTOs to drugs was correlated with individual patient's long-term postoperative prognosis, suggesting that GTOs are a good model for drug prediction for gastric cancer (GC) treatment.Varying response to chemotherapy restricts GC treatment efficacy and clinical prognosis. 1 GC-derived organoids are a good model for drug tests as they preserve primary tumour features. [2][3][4][5] However, the correlation between patients' long-term clinical prognosis and drug sensitivity is unclear. The distinction between GTOs and gastric normal organoids (GNOs) is vague. To address these questions, we established GTOs and corresponding GNOs from 17 GC patients: seven intestinal-type, eight diffuse-type and two mixed-type (Table S1). 6 Two types of GTO morphology were observed: one displaying a glandular, round pattern with an obvious lumen, similar to intestinal-type tumours; the other exhibiting a solid morphology with the nucleus shifting to one side and resembling diffuse-type tumours (Figure 1A,B). GTOs derived from mixed-type GC tissues displayed both types of morphology (Figure 1C). All GNOs derived from normal tissues displayed glandular structures, mimicking normal gastric glands (Figure 1D).To assess GTOs' tumour features, gastric tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 7 (CK7) were examined. CEA and CA19-9 expression were detected in GTO2, GTO3, GTO9, GTO13, GTO2-15, GTO10-11 and GTO10-21 and their corresponding GTs, but not in GNOs and normal tissues (Figure 1E-G and S1A-C). CEA and CA19-9 expression were found in 13 GTOs and their corresponding GTs (11/13 and 12/13, respectively) (Table S2). Therefore, GTOs preserved tumour marker expression of tumours, even in long-term cultures.