Cancer Res Treat.  2023 Oct;55(4):1077-1086. 10.4143/crt.2022.1630.

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

• Choi W
• Kim YH
• Woo SM
• Yu Y
• Lee MR
• Lee WJ
• Chun JW
• Sim SH
• Chae H
• Shim H
• Lee KS
• Kong SY

• KMID: 2547782
• DOI: http://doi.org/10.4143/crt.2022.1630

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.

Keyword

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

Figure

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  Fig. 1 (A) Representative microscopic images of organoids derived from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancer patients. Scale bars=100 μm. (B) Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer organoids. TNBC, triple-negative breast cancer. Scale bars=50 μm.

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  Fig. 2 Drug response curves for 5-fluorouracil (5-FU), irinotecan, oxaliplatin (A), and gemcitabine and nab-paclitaxel (B) in pancreatic cancer organoids. The data presented in the plot are the average of four replicate measurements of each sample.

Reference

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