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

Author:

Zhao Yuqing1,Wang Chen2,Deng Wei34,Li Lanyang2,Liu Jiping2,Shi Yanghua2,Tao Xiang1,Zhang Jian2,Cao Qi1,Cai Chunhui2,Han Xinxin25

Affiliation:

1. Obstetrics & Gynecology Hospital Fudan University Shanghai China

2. Department of Research Shanghai LiSheng Biotech Shanghai China

3. LongHua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China

4. Department of Oncology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

5. Organ Regeneration X Lab LiSheng East China Institute of Biotechnology Peking University Jiangsu China

Abstract

AbstractOvarian 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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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