Abstract
BACKGROUND: The overall treatment efficacy for gastrointestinal (GI) cancer patients with malignant ascites remains suboptimal. This study aims to construct malignant ascites-derived organoids (MADOs) that simulate the tumor characteristics of patients, thereby enabling personalized prediction of chemotherapeutic sensitivity. METHODS: Malignant ascites were collected from patients with GI malignancies for organoid culturing. The consistency between the MADOs and the in vivo tumor was assessed based on histological structure and morphology. Organoids were co-cultured with standard chemotherapy drugs. Cell viability was assessed and drug concentration-viability curves were constructed to calculate drug sensitivity. Clinical efficacy in patients was compared with the organoids drug sensitivity to comprehensively evaluate the model's effectiveness in predicting clinical outcomes. RESULTS: A total of 32 malignant ascites samples were collected for organoid culturing, with 24 cases successfully established. The MADOs exhibited high consistency with in vivo tumor tissue in terms of histological structure and morphological features. Drug sensitivity testing was performed on 14 cases with evaluable clinical efficacy. Comparison of the organoid drug sensitivity results with clinical outcomes revealed accuracy rates between 78.57% and 85.71%, sensitivity between 85.71% and 100%, and specificity between 70% and 85.71%, with Kappa values ranging from 0.571 (P=0.018) to 0.714 (P=0.008). CONCLUSIONS: Organoids derived from malignant ascites in GI malignancies have a high culturing success rate and simulate the characteristics of in vivo tumors. The drug sensitivity obtained from organoids correlates well with the clinical treatment efficacy, making them an effective model for predicting chemotherapeutic sensitivity in GI cancers with peritoneal metastasis.