Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy
Mo, Shaobo; Tang, Peiyuan; Luo, Wenqin; Zhang, Long; Li, Yaqi; Hu, Xiang; Ma, Xiaoji; Chen, Yikuan; Bao, Yichao; He, Xingfeng; Fu, Guoxiang; Xu, Xiaoya; Rao, Xinxin; Li, Xiaomeng; Guan, Ruoyu; Chen, Shengzhi; Deng, Yun; Lv, Tao; Mu, Peiyuan; Zheng, Qiang; Wang, Simin; Liu, Fangqi; Li, Yiwei; Sheng, Weiqi; Huang, Dan; Hu, Chen; Gao, Jianjun; Zhang, Zhen; Cai, Sanjun; Clevers, Hans; Peng, Junjie; Hua, Guoqiang
(2022) Advanced Science, volume 9, issue 31, pp. 1 - 16
(Article)
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
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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.
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Keywords: chemotherapy response, colorectal cancer liver metastasis, patient-derived organoid, prognosis prediction, tumor heterogeneity, Medicine (miscellaneous), General Chemical Engineering, General Materials Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), General Engineering, General Physics and Astronomy
Publisher: Wiley-VCH Verlag
Note: Funding Information: National Natural Science Foundation of China; Grant numbers 82173461 (to G.H.), U1932145 (to J.P.), 81972244 (to X.H.), 82002946 (to Y.L.); Fudan University Shanghai Cancer Center Basic and Clinical Translational Research Seed Foundation; Grant Number: YJZZ201802 (to S.C.); Science and Technology Commission of Shanghai Municipality; Grant Number: 18401933402 (to J.P.); Shanghai Sailing Program; Grant Number: 22YF1408800 (to S.M.), 19YF1409500 (to Y.L.). The authors thank colleagues from Institute of Radiation Medicine, Fudan University for their help to this work. Publisher Copyright: © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
(Peer reviewed)
