Establishment and characterization of patient-derived mucinous gastric cancer organoids with faithful histopathological features and reproducible drug response patterns.

BACKGROUND

Mucinous gastric cancer (MGC) is a rare subtype of gastric cancer (GC) characterized by distinct histological features and clinical behavior. However, the lack of specific in vitro models for MGC has hindered progress in understanding its carcinogenic mechanisms and developing effective therapeutic strategies.

METHODS

Patient-derived MGC organoids were established from paired primary tumor (MGC-T) and synchronous peritoneal metastatic nodule (MGC-ND) tissues obtained from a patient with MGC. To validate the generalizability of the findings, two additional independent MGC organoids (MGC2 and MGC3) and six non-MGC gastric cancer organoids were established in parallel under identical three-dimensional culture conditions. Histological and immunohistochemical analyses were performed to evaluate the fidelity of organoid recapitulation of parental tumor features. High-throughput drug sensitivity screening was conducted using a panel of 11 chemotherapeutic agents. Furthermore, organoid-based drug responses were correlated with the clinical outcomes of eight patients who received oxaliplatin-based adjuvant chemotherapy.

RESULTS

All MGC organoids faithfully maintained the histological architecture, mucus secretion capability, and biomarker profiles of the parental tumors over serial passages. High-throughput drug sensitivity screening revealed consistent resistance to 5-fluorouracil and oxaliplatin, and marked sensitivity to taxane-based agents, across the MGC panel. Preliminary clinical correlation in eight patients showed 87.5% concordance between organoid-based predictions and actual chemotherapy outcomes.

CONCLUSION

We established and characterized patient-derived MGC organoids from three patients, demonstrating faithful histological and molecular preservation, dynamic mucus secretion, and reproducible drug sensitivity pattern. Preliminary clinical correlation in a small cohort showed promising concordance. These proof-of-concept findings establish a platform for future precision oncology research in this rare gastric cancer subtype, pending larger prospective validation.