1. Academic Validation
  2. Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients

  • Cancer Res Treat. 2023 Jun 12. doi: 10.4143/crt.2022.1630.
Wonyoung Choi 1 2 3 Yun-Hee Kim 3 4 Sang Myung Woo 5 6 Yebeen Yu 7 Mi Rim Lee 4 Woo Jin Lee 6 8 Jung Won Chun 6 9 Sung Hoon Sim 10 11 Heejung Chae 10 12 Hyoeun Shim 13 Keun Seok Lee 1 10 Sun-Young Kong 3 7 13
Affiliations

Affiliations

  • 1 Center for Clinical Trials, National Cancer Center, Goyang, Korea.
  • 2 Division of Cancer Biology, Cancer Molecular Biology Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 3 Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Korea.
  • 4 Division of Technology Convergence, Cancer Molecular Imaging Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 5 Division of Rare and Refractory Cancer, Immuno-oncology Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 6 Center for Liver and Pancreatobiliary Cancer, Hospital, National Cancer Center, Goyang, Korea.
  • 7 Division of Rare and Refractory Cancer, Targeted Therapy Branch of Research Institute, National Cancer Center, Goyang, Korea.
  • 8 Division of Clinical Research, Cancer Outcome & Quality Improvement Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 9 Division of Clinical Research, Interventional Medicine Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 10 Center for Breast Cancer, National Cancer Center, Goyang, Korea.
  • 11 Division of Rare and Refractory Cancer, Anticancer Resistance Branch, Research Institute of National Cancer Center, Goyang, Korea.
  • 12 Center for Cancer Data Center, National Cancer Control Institute of National Cancer Center, Goyang, Korea.
  • 13 Department of Laboratory Medicine, National Cancer Center, Goyang, Korea.
Abstract

Purpose: Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.

Materials and methods: Ascitic or pleural fluid from pancreatic, gastric, and breast Cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.

Results: We collected 70 fluid samples from 58 patients (pancreatic Cancer, n=39; gastric Cancer, n=21; and breast Cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast Cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic Cancer organoids recapitulated the clinical responses of the original patients.

Conclusion: Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our Organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Keywords

Ascites; Breast neoplasms; Organoids; Pancreatic neoplasms; Pleural effusion; Stomach neoplasms.

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