ArticleOncogene2015
Integrative genomics identifies YY1AP1 as an oncogenic driver in EpCAM(+) AFP(+) hepatocellular carcinoma.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
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- United multi-omics and machine learning refine regulatory T cell-defined hepatocellular carcinoma subtypes.iScience · 2026Article
- Comprehensive transcriptomic analysis of hepatocellular Carcinoma: Uncovering shared and unique molecular signatures across diverse etiologies.Biochemistry and biophysics reports · 2025Article
- GRB2 Promotes Malignant Behaviors of Breast Cancer by Modulating the Global Expression and Alternative Splicing Profiles in SK-BR-3 Cells Through Binding mRNA.Cancer medicine · 2025Article
- A Comparative Analysis of the Roles of von Willebrand Factor and ADAMTS13 in Hepatocellular Carcinoma: A Bioinformatics and Microarray-Based Study.Current issues in molecular biology · 2025Article
- Biological roles and clinical applications of EpCAM in HCC.Discover oncology · 2025Review
- The Expression of Ferroptosis-Related Genes in Hepatocellular Carcinoma and Their Relationships With Prognosis.Journal of hepatocellular carcinoma · 2025Article
- Pure Apocrine Intraductal Carcinoma of Salivary Glands: Reassessment of Molecular Underpinnings and Behavior.Head and neck pathology · 2024Article
- Article
- Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data.Nature communications · 2022Article
- Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age.Nature communications · 2022Article
- Cancer stem cells in hepatocellular carcinoma - from origin to clinical implications.Nature reviews. Gastroenterology & hepatology · 2022Review
- Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy.Pharmacogenomics and personalized medicine · 2022Article
- Roles Played by YY1 in Embryonic, Adult and Cancer Stem Cells.Stem cell reviews and reports · 2021Review
- The pattern of gene copy number alteration (CNAs) in hepatocellular carcinoma: an in silico analysis.Molecular cytogenetics · 2021Article
- Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis.Human genomics · 2021Article
- Identification of HCC-Related Genes Based on Differential Partial Correlation Network.Frontiers in genetics · 2021Article
- Article
- Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies.World journal of gastroenterology · 2020Review
- Carcinogenetic initiation contributed by EpCAM+ cancer cells in orthotopic HCC models of immunocompetent and athymic mice.Oncotarget · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Identification of key drivers and new therapeutic targets is important given the poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those ineligible for surgical resection or liver transplant. However, the approach to identify such driver genes is facing significant challenges due to the genomically heterogenous nature of HCC. Here we tested whether the integrative genomic profiling of a well-defined HCC subset that is classified by an extreme EpCAM(+) AFP(+) gene expression signature and associated with poor prognosis, all attributes of a stem cell-like phenotype, could uncover survival-related driver genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a Gene Set Enrichment Analysis coupled with genomic copy number alteration assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical oncoprotein specifically activated in EpCAM(+) AFP(+) HCC. YY1AP1 silencing eliminates oncogene addiction by altering the chromatin landscape and triggering massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression promotes HCC proliferation and is required for the maintenance of stem cell features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin landscape and activate transcription of stemness regulators. Thus YY1AP1 may serve as a key molecular target for EpCAM(+) AFP(+) HCC subtype. Our results demonstrate the feasibility and power of a new strategy by utilizing well-defined patient samples and integrative genomics to uncover critical pathways linked to HCC subtypes with prognostic impact.
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