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Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy

Shaobo Mo, Peiyuan Tang, Wenqin Luo, Long Zhang, Yaqi Li, Xiang Hu, Xiaoji Ma, Yikuan Chen, Yichao Bao, Xingfeng He, Guoxiang Fu, Xiaoya Xu, Xinxin Rao, Xiaomeng Li, Ruoyu Guan, Shengzhi Chen, Yun Deng, Tao Lv, Peiyuan Mu, Qiang Zheng, Simin Wang, Fangqi Liu, Yiwei Li, Weiqi Sheng, Dan Huang, Chen Hu, Jianjun Gao, Zhen Zhang, Sanjun Cai, Hans Clevers, Junjie Peng, Guoqiang Hua

Published: 2022

Abstract

There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

Full Access Link: Advanced Science