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Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma

 Hyungjin Rhee  ;  Jung Eun Ko  ;  Taek Chung  ;  Byul A Jee  ;  So Mee Kwon  ;  Ji Hae Nahm  ;  Jae Yeon Seok  ;  Jeong Eun Yoo  ;  Jin-Sub Choi  ;  Snorri S Thorgeirsson  ;  Jesper B Andersen  ;  Hye Sun Lee  ;  Hyun Goo Woo  ;  Young Nyun Park 
 Liver International, Vol.38(1) : 113-124, 2018 
Journal Title
 Liver International 
Issue Date
CRP ; CDH2 ; S100P ; TFF1 ; cholangiolocellular differentiation
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome-wide molecular features and clinical significance remain unclear. METHODS: Based on CD status, we stratified iCCAs into iCCA with CD (n=20) and iCCA without CD (n=102), and performed an integrative analysis using transcriptomic and clinicopathological profiles. RESULTS: iCCA with CD revealed less aggressive histopathological features compared to iCCA without CD, and iCCA with CD showed favourable clinical outcomes of overall survival and time to recurrence than iCCA without CD (P<.05 for all). Transcriptomic profiling revealed that iCCA with CD resembled an inflammation-related subtype, while iCCA without CD resembled a proliferation subtype. In addition, we identified a CD signature that can predict prognostic outcomes of iCCA (CD_UP, n=486 and CD_DOWN, n=308). iCCAs were subgrouped into G1 (positivity for CRP and CDH2, 7%), G3 (positivity for S100P and TFF1, 32%) and G2 (the others, 61%). Prognostic outcomes for overall survival (P=.001) and time to recurrence (P=.017) were the most favourable in G1-iCCAs, intermediate in G2-iCCAs and the worst in G3-iCCAs. Similar result was confirmed in the iCCA set from GSE26566 (n=68). CONCLUSIONS: CD signature was identified to predict the prognosis of iCCA. The combined evaluation of histology of CD and protein expression status of CRP, CDH2, TFF1 and S100P might help subtyping and predicting clinical outcomes of iCCA.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
남지해(Nahm, Ji Hae) ORCID logo https://orcid.org/0000-0003-0902-866X
박영년(Park, Young Nyun) ORCID logo https://orcid.org/0000-0003-0357-7967
석재연(Seok, Jae Yeon)
유정은(Yoo, Jeong Eun)
이형진(Rhee, Hyungjin) ORCID logo https://orcid.org/0000-0001-7759-4458
이혜선(Lee, Hye Sun) ORCID logo https://orcid.org/0000-0001-6328-6948
정택(Chung, Taek) ORCID logo https://orcid.org/0000-0001-7567-0680
최진섭(Choi, Jin Sub)
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