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KMID : 1188320220160040625
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Gut and Liver
2022 Volume.16 No. 4 p.625 ~ p.636
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Establishment of Patient-Derived Pancreatic Cancer Organoids from Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsies
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Lee Jee-Hyung
Kim Hae-Ryoung
Lee Sang-Hyub
Ku Ja-Lok
Chun Jung-Won
Seo Ha-Young
Kim Soon-Chan
Paik Woo-Hyun
Ryu Ji-Kon
Lee Sang-Kook
Lowy Andrew M.
Kim Yong-Tae
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Abstract
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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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KEYWORD
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Pancreatic neoplasms, Endoscopic ultrasound-guided fine-needle aspiration, Organoid, High-throughput nucleotide sequencing, FOLFIRINOX
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