Cancer Research and Treatment

Original Articles

General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

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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.

Citations

Citations to this article as recorded by

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
Cell Reports Medicine.2024; 5(3): 101461. CrossRef
Establishment and Advancement of Pancreatic Organoids
Dong Hyeon Lee
Keimyung Medical Journal.2024; 43(1): 3. CrossRef
Organoid as a promising tool for primary liver cancer research: a comprehensive review
Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
Cell & Bioscience.2024;[Epub] CrossRef
The use of organoids in creating immune microenvironments and treating gynecological tumors
Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
Journal of Translational Medicine.2024;[Epub] CrossRef
Organoid: Bridging the gap between basic research and clinical practice
Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
Cancer Letters.2023; 572: 216353. CrossRef

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Gastrointestinal cancer

Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma: Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1303-1312. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.291

Abstract PDF Supplementary Material PubReader ePub

Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Citations

Citations to this article as recorded by

MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C
Wen-Jing Liu, Jun Lu, Wei-Xun Zhou, Jian-Zhou Liu, Li Zhou
Laboratory Investigation.2024; 104(9): 102107. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
Laboratory Medicine Online.2024; 14(4): 311. CrossRef
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
Antonino Pantaleo, Giovanna Forte, Candida Fasano, Martina Lepore Signorile, Paola Sanese, Katia De Marco, Elisabetta Di Nicola, Marialaura Latrofa, Valentina Grossi, Vittoria Disciglio, Cristiano Simone
Cancers.2023; 16(1): 56. CrossRef

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