A platform for efficient establishment and drug response profiling of high-grade serous ovarian cancer organoids. A platform for efficient establishment and drug response profiling of high-grade serous ovarian cancer organoids

The broad research use of organoids from high-grade serous ovarian carcinoma (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (53% vs. 23-38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research. Overall design: This study includes scRNAseq data from 7 HGSOC patient-derived organoids and their tumor tissue/ascites of origin. ----------------------------- Authors state "The raw data has been uploaded to EGA(EGAS00001006246) in order to comply with data protection regulations".

高级别浆液性卵巢癌（high-grade serous ovarian carcinoma, HGSC）类器官的广泛研究应用长期受到培养成功率偏低与新鲜肿瘤组织材料可及性不足的制约。本研究报道了一种可高效生成并长期扩增HGSC类器官的方法，其培养效率较既往研究显著提升，成功率达53%，而既往报道的成功率仅为23%~38%。我们可通过冻存组织样本建立类器官，证实了利用可存活的生物样本库组织构建HGSC类器官的可行性。基因组学、组织学以及单细胞转录组学分析显示，该类器官能够重现原始肿瘤的遗传与表型特征。类器官的药物反应与临床治疗结局具有相关性，但该相关性呈现培养条件依赖性，且仅在以人血浆样培养基（human plasma-like medium, HPLM）培养的类器官中可观测到。签署知情同意书的患者来源类器官可通过公共生物样本库向科研社群开放，其类器官基因组数据可通过交互式在线工具进行查询探索。综上，本研究资源可为HGSC类器官在基础与转化卵巢癌研究中的应用提供有力支持。
整体实验设计：本研究涵盖7例HGSC患者来源类器官及其来源肿瘤组织/腹水的单细胞RNA测序（scRNAseq）数据。
作者声明："为遵守数据保护法规，原始数据已上传至欧洲基因组表型档案库（European Genome-phenome Archive, EGA，EGAS00001006246）。"