Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies
Jee Hyung Lee,
Haeryoung Kim,
Sang Hyub Lee,
Ja-Lok Ku,
Jung Won Chun,
Ha Young Seo,
Soon Chan Kim,
Woo Hyun Paik,
Ji Kon Ryu,
Sang Kook Lee,
Andrew M. Lowy,
Yong-Tae Kim
Affiliations
Jee Hyung Lee
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Haeryoung Kim
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Sang Hyub Lee
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Ja-Lok Ku
Department of Biomedical Sciences, Korean Cell Line Bank, Laboratory of Cell Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Jung Won Chun
Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
Ha Young Seo
Department of Biomedical Sciences, Korean Cell Line Bank, Laboratory of Cell Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Soon Chan Kim
Department of Biomedical Sciences, Korean Cell Line Bank, Laboratory of Cell Biology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Woo Hyun Paik
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Ji Kon Ryu
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Sang Kook Lee
Natural Products Research Institute, Seoul National University College of Pharmacy, Seoul, Korea
Andrew M. Lowy
Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
Yong-Tae Kim
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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.
