doctor Hualien Tzu Chi Hospital, Tzu Chi University Hualien, Hualien, Taiwan (Republic of China)
Abstract: This study aimed to evaluate the utility of ovarian cancer patient-derived organoids (PDOs) in replicating genetic characteristics and assessing drug responsiveness. PDOs were cultured in Matrigel using a specialized medium, and success rates and proliferation rates were analyzed. Morphology, histology, and immunohistochemistry (IHC) markers (PAX8, P53, and WT1) were employed to identify tumor characteristics. Genetic profiling was conducted through gene sequencing, variant allele frequency (VAF) analysis, and copy number variation assessment. Drug sensitivity testing was performed with carboplatin, paclitaxel, gemcitabine, doxorubicin, and olaparib. Organoids were successfully generated in 54% (7/13) of cases, including 4 high-grade serous carcinomas (HGSC), 1 mucinous carcinoma (MC), 1 clear cell carcinoma (CCC), and 1 carcinosarcoma. Six organoids (3 HGSC, 1 CCC, 1 MC, and 1 carcinosarcoma) were used in subsequent experiments. The organoids exhibited spherical morphology with diameters ranging from 100 to 500 μm. Histological and IHC analyses confirmed that organoids retained characteristics consistent with their corresponding primary tumors. After cryopreservation, organoid proliferation was slower compared to primary cultures (14 days vs. 10 days, P < 0.01). Targeted sequencing revealed shared DNA variants between primary tumors and organoids, including mutations in key genes such as BRCA1, PIK3CA, ARID1A, and TP53. VAF analysis demonstrated similarity between organoids and primary tumors, and organoids preserved most copy number alterations. Drug sensitivity tests showed differential responses, with carcinosarcoma organoids exhibiting higher sensitivity to paclitaxel and gemcitabine compared to HGSC organoids. These preliminary findings demonstrate that ovarian cancer PDOs can be successfully established, faithfully replicating histological features, genetic mutations, and copy number variations of primary tumors. Drug testing on PDOs revealed individualized drug responses, underscoring their potential as valuable resources for investigating genomic biomarkers and advancing personalized cancer therapy.
Funding Source: National Science and Technology Council (NSTC 111-2314-B-303-019 and 112-2314-B-303-010-MY3)
