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Ubiquitin-specific protease 11 serves as a marker of poor prognosis and promotes metastasis in hepatocellular carcinoma.
- Source :
-
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2018 Jul; Vol. 98 (7), pp. 883-894. Date of Electronic Publication: 2018 Mar 15. - Publication Year :
- 2018
-
Abstract
- Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo. A large body of evidence supports a link between UPS11 and tumorigenesis. However, the clinical significance and biological function of USP11 in hepatocellular carcinoma (HCC) remains unclear. Here, USP11 expression was assessed by immunohistochemistry in a pilot series of 71 HCC clinical samples, and the association between USP11 expression and clinicopathological features and overall survival time was analyzed. The cytoplasmic expression rate of USP11 was higher in non-cancerous tissue than that in cancer tissue (36.6 vs. 12.7%, P = 0.001), whereas the nuclear expression rate of USP11 was lower in non-cancerous tissue (5.6 vs. 69.0%, P < 0.001). USP11 expression level was higher in tumor than that in non-tumor tissue (P < 0.001). Chi-square analysis of variances suggested that USP11 expression was associated with vascular invasion (P = 0.033), differentiation (P = 0.027), tumor number (P = 0.009), and recurrence (P = 0.036). USP11 expression was also associated with shorter overall survival time (P = 0.001) by log-rank test. Unconditional logistic regression analysis with multiple covariates indicated that high USP11 expression was associated with a 2.96-fold increase in the risk of death compared with low USP11 levels (P = 0.041) and acted as an independent predictor of overall survival. HCC patients with simultaneously high USP11 and alpha-fetoprotein expression had an adjusted 5-fold higher risk of all-cause-related death (P = 0.006). Moreover, in vitro and in vivo experiments confirmed that USP11 could promote the migration and invasion of HCC cell. Overall, we suggest that USP11 promotes HCC cell metastasis, and we provide the first evidence of the prognostic significance of USP11 expression in HCC, which suggests that USP11 is a promising therapeutic target for the treatment of HCC.
- Subjects :
- Adult
Aged
Aged, 80 and over
Animals
Biomarkers, Tumor analysis
Carcinoma, Hepatocellular chemistry
Carcinoma, Hepatocellular mortality
Cell Line, Tumor
Female
Gene Knockdown Techniques
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Liver Neoplasms chemistry
Liver Neoplasms mortality
Male
Mice
Mice, Nude
Middle Aged
Prognosis
Signal Transduction physiology
Thiolester Hydrolases analysis
Thiolester Hydrolases genetics
Young Adult
Biomarkers, Tumor metabolism
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Liver Neoplasms metabolism
Liver Neoplasms pathology
Thiolester Hydrolases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0307
- Volume :
- 98
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Type :
- Academic Journal
- Accession number :
- 29545598
- Full Text :
- https://doi.org/10.1038/s41374-018-0050-7