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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number237
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology

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