Gut Liver.
2022 Jul;16(4):625-636. 10.5009/gnl210166.
Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies
- Affiliations
-
- 1Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
- 2Natural Products Research Institute, Seoul National University College of Pharmacy, Seoul, Korea.
- 3Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
- 4Department of Biomedical Sciences, Korean Cell Line Bank, Laboratory of Cell Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
- 5Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea.
- 6Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
- KMID: 2531245
- DOI: http://doi.org/10.5009/gnl210166
Abstract
- Background/Aims
Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research.
Methods
Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays.
Results
Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy.
Conclusions
The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research
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