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Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma
Author(s) -
Rhee Hyungjin,
Ko Jung Eun,
Chung Taek,
Jee Byul A,
Kwon So Mee,
Nahm Ji Hae,
Seok Jae Yeon,
Yoo Jeong Eun,
Choi JinSub,
Thorgeirsson Snorri S.,
Andersen Jesper B.,
Lee Hye Sun,
Woo Hyun Goo,
Park Young Nyun
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13492
Subject(s) - intrahepatic cholangiocarcinoma , transcriptome , inflammation , medicine , histology , phenotype , pathology , gastroenterology , biology , oncology , gene , gene expression , genetics
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 iCCA s 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). iCCA s were subgrouped into G1 (positivity for CRP and CDH 2, 7%), G3 (positivity for S100P and TFF 1, 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‐ iCCA s, intermediate in G2‐ iCCA s and the worst in G3‐ iCCA s. 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 , CDH 2, TFF 1 and S100P might help subtyping and predicting clinical outcomes of iCCA .