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Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma

Authors
Rhee, H; Ko, JE; Chung, T; Jee, BA; Kwon, SM; Nahm, JH; Seok, JY; Yoo, JE; Choi, JS; Thorgeirsson, SS; Andersen, JB; Lee, HS; Woo, HG; Park, YN
Citation
Liver international : official journal of the International Association for the Study of the Liver, 38(1):113-124, 2018
Journal Title
Liver international : official journal of the International Association for the Study of the Liver
ISSN
1478-32231478-3231
Abstract
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.
Keywords
CDH2cholangiolocellular differentiationCRPS100PTFF1
MeSH terms
AgedBile Duct Neoplasms/chemistryBile Duct Neoplasms/genetics*Bile Duct Neoplasms/pathology*Biomarkers, Tumor/analysisBiomarkers, Tumor/genetics*Cell Differentiation/genetics*Cell Proliferation/geneticsCholangiocarcinoma/chemistryCholangiocarcinoma/genetics*Cholangiocarcinoma/pathology*FemaleGene Expression Profiling/methods*Gene Expression Regulation, NeoplasticHumansImmunohistochemistryMaleMiddle AgedPhenotypePredictive Value of TestsPrognosisRisk FactorsTissue Array AnalysisTranscriptome
DOI
10.1111/liv.13492
PMID
28608943
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
지, 별아권, 소미우, 현구
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