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

Adv Sci (Weinh). 2022 Nov;9(31):e2204097. doi: 10.1002/advs.202204097. Epub 2022 Sep 4.

Authors

Shaobo Mo^{1

2}, Peiyuan Tang³, Wenqin Luo^{1

2}, Long Zhang^{1

2

4}, Yaqi Li^{1

2}, Xiang Hu^{1

2}, Xiaoji Ma^{1

2}, Yikuan Chen^{1

2}, Yichao Bao^{1

2}, Xingfeng He^{1

2}, Guoxiang Fu⁵, Xiaoya Xu³, Xinxin Rao³, Xiaomeng Li³, Ruoyu Guan³, Shengzhi Chen³, Yun Deng^{2

3

6}, Tao Lv^{2

6}, Peiyuan Mu^{2

6}, Qiang Zheng^{2

7}, Simin Wang^{2

8}, Fangqi Liu^{1

2}, Yiwei Li^{1

2}, Weiqi Sheng^{2

7}, Dan Huang^{2

7}, Chen Hu⁹, Jianjun Gao³, Zhen Zhang^{2

6}, Sanjun Cai^{1

2

4}, Hans Clevers¹⁰, Junjie Peng^{1

2}, Guoqiang Hua^{4

6}

Affiliations

¹ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
³ Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China.
⁴ Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
⁵ Research and Early Development, D1Med Technology (Shanghai) Inc, Shanghai, 200235, P. R. China.
⁶ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, P. R. China.
⁷ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
⁸ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
⁹ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
¹⁰ Hubrecht Institute, KNAW and University Medical Center Utrecht, P.O. Box 85500, Utrecht, 3584 CT, The Netherlands.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
Humans
Liver Neoplasms* / drug therapy
Organoids
Prognosis

Substances

Antineoplastic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding