Patient-derived ovarian cancer organoid carries immune microenvironment and blood vessel keeping high response to cisplatin

患者来源的卵巢癌类器官携带免疫微环境和血管,对顺铂保持高反应

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作者:Yuqing Zhao, Chen Wang, Wei Deng, Lanyang Li, Jiping Liu, Yanghua Shi, Xiang Tao, Jian Zhang, Qi Cao, Chunhui Cai, Xinxin Han

Abstract

Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian cancer was High-Grade Serous Ovarian Cancer. However, High-Grade Serous Ovarian Cancer organoid is rare, which organoid with patient immune microenvironment and blood vessels even absence. Here, we report a novel High-Grade Serous Ovarian Cancer organoid system derived from patient ovarian cancer samples. These organoids recapitulate High-Grade Serous Ovarian Cancer organoids' histological and molecular heterogeneity while preserving the critical immune microenvironment and blood vessels, as evidenced by the presence of CD34 + endothelial cells. Whole exome sequencing identifies key mutations (CSMD3, TP53, GABRA6). Organoids show promise in testing cisplatin sensitivity for patients resistant to carboplatin and paclitaxel, with notable responses in cancer proteoglycans and p53 (TP53) signaling, like ACTG/ACTB1/AKT2 genes and BBC3/MDM2/PERP. Integration of immune microenvironment and blood vessels enhances potential for novel therapies like immunotherapies and angiogenesis inhibitors. Our work may provide a new detection system and theoretical basis for ovarian cancer research and individual therapy.

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