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Molecular and radiopathologic spectrum between HCC and intrahepatic cholangiocarcinoma

 Youngsic Jeon  ;  So Mee Kwon  ;  Hyungjin Rhee  ;  Jeong Eun Yoo  ;  Taek Chung  ;  Hyun Goo Woo  ;  Young Nyun Park 
 HEPATOLOGY, Vol.77(1) : 92-108, 2023-01 
Journal Title
Issue Date
Bile Duct Neoplasms* / diagnostic imaging ; Bile Duct Neoplasms* / genetics ; Bile Duct Neoplasms* / metabolism ; Bile Ducts, Intrahepatic / pathology ; Carcinoma, Hepatocellular* / diagnostic imaging ; Carcinoma, Hepatocellular* / genetics ; Carcinoma, Hepatocellular* / metabolism ; Cholangiocarcinoma* / diagnostic imaging ; Cholangiocarcinoma* / genetics ; Cholangiocarcinoma* / metabolism ; Humans ; Liver Neoplasms* / diagnostic imaging ; Liver Neoplasms* / genetics ; Liver Neoplasms* / metabolism
Background and aims: Primary liver cancers (LCs), including HCC and intrahepatic cholangiocarcinoma (iCCA), are derived from a common developmental lineage, conferring a molecular spectrum between them. To elucidate the molecular spectrum, we performed an integrative analysis of transcriptome profiles associated with patients' radiopathologic features.

Approach and results: We identified four LC subtypes (LC1-LC4) from RNA-sequencing profiles, revealing intermediate subtypes between HCC and iCCA. LC1 is a typical HCC characterized by active bile acid metabolism, telomerase reverse transcriptase promoter mutations, and high uptake of gadoxetic acid in MRI. LC2 is an iCCA-like HCC characterized by expression of the progenitor cell-like trait, tumor protein p53 mutations, and rim arterial-phase hyperenhancement in MRI. LC3 is an HCC-like iCCA, mainly small duct (SD) type, associated with HCC-related etiologic factors. LC4 is further subclassified into LC4-SD and LC4-large duct iCCAs according to the pathological features, which exhibited distinct genetic variations (e.g., KRAS , isocitrate dehydrogenase 1/2 mutation, and FGF receptor 2 fusion), stromal type, and prognostic outcomes.

Conclusions: Our integrated view of the molecular spectrum of LCs can identify subtypes associated with transcriptomic, genomic, and radiopathologic features, providing mechanistic insights into heterogeneous LC progression.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Rhee, Hyungjin(이형진) ORCID logo https://orcid.org/0000-0001-7759-4458
Chung, Taek(정택) ORCID logo https://orcid.org/0000-0001-7567-0680
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