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

doi:10.1002/advs.202204097

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 ZhengSimin Wang, Fangqi Liu, Yiwei Li, Weiqi Sheng, Dan Huang, Chen Hu, Jianjun Gao, Zhen Zhang, Sanjun Cai, Hans Clevers, Junjie Peng^*, Guoqiang Hua

^*Corresponding author for this work

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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.

Original language	English
Article number	2204097
Pages (from-to)	1-16
Journal	Advanced Science
Volume	9
Issue number	31
DOIs	https://doi.org/10.1002/advs.202204097
Publication status	Published - 3 Nov 2022

Keywords

chemotherapy response
colorectal cancer liver metastasis
patient-derived organoid
prognosis prediction
tumor heterogeneity

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10.1002/advs.202204097Licence: CC BY

Advanced Science - 2022 - Mo - Patient‐Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal TumorFinal published version, 6.49 MBLicence: CC BY

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Mo, S., Tang, P., Luo, W., Zhang, L., Li, Y., Hu, X., Ma, X., Chen, Y., Bao, Y., He, X., Fu, G., Xu, X., Rao, X., Li, X., Guan, R., Chen, S., Deng, Y., Lv, T., Mu, P., ... Hua, G. (2022). Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy. Advanced Science, 9(31), 1-16. Article 2204097. https://doi.org/10.1002/advs.202204097

@article{70b856d3d3ce4954999bf58007f8c3cd,

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

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.",

keywords = "chemotherapy response, colorectal cancer liver metastasis, patient-derived organoid, prognosis prediction, tumor heterogeneity",

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

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: {\textcopyright} 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.",

year = "2022",

month = nov,

day = "3",

doi = "10.1002/advs.202204097",

language = "English",

volume = "9",

pages = "1--16",

journal = "Advanced Science",

publisher = "Wiley-VCH Verlag",

number = "31",

}

Mo, S, Tang, P, Luo, W, Zhang, L, Li, Y, Hu, X, Ma, X, Chen, Y, Bao, Y, He, X, Fu, G, Xu, X, Rao, X, Li, X, Guan, R, Chen, S, Deng, Y, Lv, T, Mu, P, Zheng, Q, Wang, S, Liu, F, Li, Y, Sheng, W, Huang, D, Hu, C, Gao, J, Zhang, Z, Cai, S, Clevers, H, Peng, J & Hua, G 2022, 'Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy', Advanced Science, vol. 9, no. 31, 2204097, pp. 1-16. https://doi.org/10.1002/advs.202204097

TY - JOUR

T1 - Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy

AU - Mo, Shaobo

AU - Tang, Peiyuan

AU - Luo, Wenqin

AU - Zhang, Long

AU - Li, Yaqi

AU - Hu, Xiang

AU - Ma, Xiaoji

AU - Chen, Yikuan

AU - Bao, Yichao

AU - He, Xingfeng

AU - Fu, Guoxiang

AU - Xu, Xiaoya

AU - Rao, Xinxin

AU - Li, Xiaomeng

AU - Guan, Ruoyu

AU - Chen, Shengzhi

AU - Deng, Yun

AU - Lv, Tao

AU - Mu, Peiyuan

AU - Zheng, Qiang

AU - Wang, Simin

AU - Liu, Fangqi

AU - Li, Yiwei

AU - Sheng, Weiqi

AU - Huang, Dan

AU - Hu, Chen

AU - Gao, Jianjun

AU - Zhang, Zhen

AU - Cai, Sanjun

AU - Clevers, Hans

AU - Peng, Junjie

AU - Hua, Guoqiang

N1 - 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.

PY - 2022/11/3

Y1 - 2022/11/3

N2 - 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.

AB - 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.

KW - chemotherapy response

KW - colorectal cancer liver metastasis

KW - patient-derived organoid

KW - prognosis prediction

KW - tumor heterogeneity

UR - http://www.scopus.com/inward/record.url?scp=85137355207&partnerID=8YFLogxK

U2 - 10.1002/advs.202204097

DO - 10.1002/advs.202204097

M3 - Article

C2 - 36058001

AN - SCOPUS:85137355207

VL - 9

SP - 1

EP - 16

JO - Advanced Science

JF - Advanced Science

IS - 31

M1 - 2204097

ER -

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

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