한빛사논문
- 조회431
Hee Seung Lee1,2,5, Dai Hoon Han2,3,5, Kyungjoo Cho1, Soo Been Park1, Chanyang Kim1, Galam Leem1, Dawoon E. Jung1,2, Soon Sung Kwon4, Chul Hoon Kim4, Jung Hyun Jo1,2, Hye Won Lee1,2, Si Young Song1,2,6 & Jun Yong Park1,2,6
1Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
2Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
3Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
4Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
5These authors contributed equally:Hee Seung Lee, Dai Hoon Han.
6These authors jointly supervised this work: Si Young Song, Jun Yong Park.
Corresponding authors: Correspondence to Si Young Song or Jun Yong Park.
Abstract
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.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-01-18)
- 국내 연구진
- 의약학 > 응용의학
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