Patient-derived organoid cultures model human primary liver cancer in vitro. Homo sapiens

The study of human liver cancer has been hampered by the lack of reliable models that faithfully recapitulate the physiopathology of the patient’s original tumour ex vivo. Here, we describe the first culture system to allow the establishment and long-term expansion of human primary liver cancer (PLC) organoids (called tumoroids) from the three most common PLC subtypes: Hepatocellular carcinoma (HCC), Cholangiocarcinoma (CC) and mixed HCC/CC tumours (CHC). We evaluated whether tumoroid lines maintain the expression profile and the genomic landscape of the original tumor they derived from by performing genome-wide (RNAseq/WES) analyses before and after culture. These analyses reveal that the cultures closely recapitulate the gene expression and the mutational landscape of the original tumor, allowing discrimination between different tumor subtypes (HCC, CHC, CC). Overall design: We generated RNAseq and WES data from healthy donor and 7 tumoral human PLC tissues and their derived organoid cultures maintained in our defined medium.

人类肝癌研究长期受限于缺乏能够在体外（ex vivo）忠实重现患者原发肿瘤病理生理学特征的可靠模型。本研究首次报道了一种培养体系，可从三种最常见的人类原发性肝癌（PLC）亚型——肝细胞癌（HCC）、胆管癌（CC）以及混合肝细胞癌/胆管癌（CHC）——中建立并长期扩增人源原发性肝癌类器官（tumoroids，又称肿瘤类器官）。我们通过在培养前后开展全基因组层面的RNA测序（RNAseq）与全外显子测序（WES）分析，评估了肿瘤类器官系是否能够保留其来源原发肿瘤的表达谱与基因组特征。分析结果显示，该培养体系可精准重现原发肿瘤的基因表达与突变图谱，能够有效区分不同的肿瘤亚型（HCC、CHC、CC）。实验整体设计：我们从健康供体、7例人源原发性肝癌肿瘤组织及其在本研究使用的限定培养基中维持培养的类器官系中，获取了RNAseq与WES数据。