계명대학교 의학도서관 Repository

Consensus subtypes of hepatocellular carcinoma associated with clinical outcomes and genomic phenotypes

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Author(s)
Sung Hwan LeeSun Young YimYun Seong JeongQi-Xiang LiSang-Hee KangBo Hwa SohnShwetha V. KumarJi-Hyun ShinYou Rhee ChoiJae-Jun ShimHayeon KimJihoon KimShin KimSheng GuoRandy L. JohnsonAhmed KasebKoo Jeong KangYun Shin ChunHee Jin JangByoung Gill LeeHyun Goo WooMin Jin HaRehan AkbaniLewis R. RobertsDavid A. WheelerJu-Seog Lee
Keimyung Author(s)
Kim, ShinKang, Koo Jeong
Department
Dept. of Immunology (면역학)
Dept. of Surgery (외과학)
Journal Title
Hepatology
Issued Date
2022
Volume
76
Issue
6
Abstract
Background & aims:
While many studies revealed transcriptomic subtypes of hepatocellular carcinoma (HCC), concordance of the subtypes are not fully examined. We aim to examine consensus of transcriptomic subtypes and correlate them with clinical outcomes.

Approach and results:
By integrating 16 previously established genomic signatures for HCC subtypes, we identified 5 clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male predominance) is characterized by prominent β-catenin activation, low miRNA expression, hypomethylation, and high sensitivity to sorafenib. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. We also developed and validated a robust predictor of consensus subtype with 100 genes (PICS100) and demonstrated that 5 subtypes were well conserved in patient derived xenograft (PDX) models and cell lines. By analyzing serum proteomic data from the same patients, we further identified potential serum biomarkers that can stratify patients into subtypes.

Conclusions:
Five HCC subtypes are correlated with genomic phenotypes and clinical outcomes and highly conserved in pre-clinical models, providing a framework for selecting the most appropriate models for preclinical studies.
Keimyung Author(s)(Kor)
김신
강구정
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1527-3350
Source
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32490
DOI
10.1002/hep.32490
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44695
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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