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Cited 17 time in webofscience Cited 16 time in scopus
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Low ARID1A Expression is Associated with Poor Prognosis in Hepatocellular Carcinoma

Authors
Yim, Sun YoungKang, Sang HeeShin, Ji-HyunJeong, Yun SeongSohn, Bo HwaUm, Soon HoLee, Ju-Seog
Issue Date
Sep-2020
Publisher
Multidisciplinary Digital Publishing Institute (MDPI)
Keywords
ARID1A; hepatocellular carcinoma; genomics; prognosis
Citation
Cells, v.9, no.9
Indexed
SCIE
SCOPUS
Journal Title
Cells
Volume
9
Number
9
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/32904
DOI
10.3390/cells9092002
ISSN
2073-4409
Abstract
AT-rich interactive domain 1A (ARID1A) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), but its clinical significance is not clarified. We aimed to evaluate the clinical significance of lowARID1Aexpression in HCC. By analyzing the gene expression data of liver fromArid1a-knockout mice, hepaticArid1a-specific gene expression signature was identified (p< 0.05 and 0.5-fold difference). From this signature, a prediction model was developed to identify tissues lackingArid1aactivity and was applied to gene expression data from three independent cohorts of HCC patients to stratify patients according toARID1Aactivity. The molecular features associated with loss ofARID1Awere analyzed using The Cancer Genome Atlas (TCGA) multi-platform data, and Ingenuity Pathway Analysis (IPA) was done to uncover potential signaling pathways associated withARID1Aloss.ARID1Ainactivation was clinically associated with poor prognosis in all three independent cohorts and was consistently related to poor prognosis subtypes of previously reported gene signatures (highly proliferative, hepatic stem cell, silence of Hippo pathway, and high recurrence signatures). Immune activity, indicated by significantly lower IFNG6 and cytolytic activity scores and enrichment of regulatory T-cell composition, was lower in theARID1A-low subtype thanARID1A-high subtype. Ingenuity pathway analysis revealed that direct upstream transcription regulators of theARID1Asignature were genes associated with cell cycle, includingE2Fgroup,CCND1,andMYC,while tumor suppressors such asTP53, SMAD3,andCTNNB1were significantly inhibited.ARID1Aplays an important role in immune activity and regulating multiple genes involved in HCC development. Low-ARID1Asubtype was associated with poor clinical outcome and suggests the possibility ofARID1Aas a prognostic biomarker in HCC patients.
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2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles
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Kang, Sang hee
구로병원 (Department of Colon and Rectal Surgery, Guro Hospital)
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