ArticlePloS one2014
Nuclear expression of the deubiquitinase CYLD is associated with improved survival in human hepatocellular carcinoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Targeting noncanonical nuclear factor kappa B signalling in CYLD cutaneous syndrome by selective inhibition of IκB kinase alpha.The British journal of dermatology · 2026Article
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Suppression of CYLD by HER3 confers ovarian cancer platinum resistance via inhibiting apoptosis and by inducing drug efflux.Experimental hematology & oncology · 2025Article
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- Down-regulated cylindromatosis enhances NF-κB activation and aggravates inflammation in HBV-ACLF patients.Emerging microbes & infections · 2022Article
- Article
- Expression of the deubiquitinase cylindromatosis in articular cartilage and subchondral bone is associated with the severity of knee osteoarthritis.Experimental and therapeutic medicine · 2017Article
- Cylindromatosis Tumor Suppressor Protein (CYLD) Deubiquitinase is Necessary for Proper Ubiquitination and Degradation of the Epidermal Growth Factor Receptor.Molecular & cellular proteomics : MCP · 2017Article
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Authors and funding
14 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe deubiquitinase CYLD removes (K-63)-linked polyubiquitin chains from proteins involved in NF-κB, Wnt/ß-catenin and Bcl-3 signaling. Reduced CYLD expression has been reported in different tumor entities, including hepatocellular carcinoma (HCC). Furthermore, loss of CYLD has been shown to contribute to HCC development in knockout animal models. This study aimed to assess subcellular CYLD expression in tumor tissues and its prognostic significance in HCC patients undergoing liver resection or liver transplantation.
methodsSubcellular localization of CYLD was assessed by immunohistochemistry in tumor tissues of 95 HCC patients undergoing liver resection or transplantation. Positive nuclear CYLD staining was defined as an immunohistochemical (IHC) score ≥ 3. Positive cytoplasmic CYLD staining was defined as an IHC score ≥ 6. The relationship with clinicopathological parameters was investigated. Cell culture experiments were performed to analyze subcellular CYLD expression in vitro.
resultsCytoplasmic CYLD expression was observed in 57 out of 95 (60%) HCC specimens (cyt°CYLD+). Nuclear CYLD staining was positive in 52 out of 95 specimens (55%, nucCYLD+). 13 out of 52 nucCYLD+ patients (25%) showed a lack of cytoplasmic CYLD expression. nucCYLD+ was associated with prolonged overall survival in patients after resection or liver transplantation (P = 0.007). 5-year overall survival rates were 63% in nucCYLD+ vs. 26% in nucCYLD- patients. Nuclear CYLD staining strongly correlated with tumor grading (P<0.001) and Ki67 positivity (P = 0.005). nucCYLD+ did not prove to be an independent prognostic parameter. In vitro, Huh7, Hep3B and HepG2 showed reduced CYLD levels compared to the non-malignant liver cell line THLE-2. Induction of CYLD expression by doxorubicin treatment led to increased cytoplasmic and nuclear expression of CYLD.
conclusionsExpression of nuclear CYLD is a novel prognostic factor for improved survival in patients with HCC undergoing liver resection or transplantation.
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