Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies
J.H. 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
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: 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.