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Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping

 Hee Seung Lee  ;  Dai Hoon Han  ;  Kyungjoo Cho  ;  Soo Been Park  ;  Chanyang Kim  ;  Galam Leem  ;  Dawoon E Jung  ;  Soon Sung Kwon  ;  Chul Hoon Kim  ;  Jung Hyun Jo  ;  Hye Won Lee  ;  Si Young Song  ;  Jun Yong Park 
 NATURE COMMUNICATIONS, Vol.14(1) : 237, 2023-01 
Journal Title
Issue Date
Bile Duct Neoplasms* / genetics ; Bile Duct Neoplasms* / pathology ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma* / metabolism ; Genomics ; Humans ; Prospective Studies
As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lee, Hye Won(이혜원) ORCID logo https://orcid.org/0000-0002-3552-3560
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Leem, Ga Lam(임가람)
Jung, Dawoon E.(정다운)
Jo, Jung Hyun(조중현) ORCID logo https://orcid.org/0000-0002-2641-8873
Han, Dai Hoon(한대훈) ORCID logo https://orcid.org/0000-0003-2787-7876
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