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Journal of Cellular and Molecular... Mar 2021c-Jun activation domain-binding protein-1 (Jab1) is aberrantly overexpressed in multiple cancers and plays an oncogenic role in cancer progression. We examined the... (Meta-Analysis)
Meta-Analysis
c-Jun activation domain-binding protein-1 (Jab1) is aberrantly overexpressed in multiple cancers and plays an oncogenic role in cancer progression. We examined the association between Jab1 expression and prognosis in patients with cancer by conducting a meta-analysis. A comprehensive search strategy was performed using the PubMed, Web of Science, Ovid and EMBASE in July 2020. Eligible studies were enrolled according to definite criteria. Twenty-seven studies involving 2609 patients were enrolled in this meta-analysis. A significant association between high Jab1 expression and poor overall survival (pooled hazard ratio [HR] 2.344, 95% confidence interval [CI]: 2.037-2.696) was observed. Subgroup analyses of the type of cancer, sample size, follow-up period, Jab1 detection method and preoperative treatment did not alter the significance. On pooling data from Cox multivariate analyses, high Jab1 expression was found to be an independent prognostic indicator for overall survival. In addition, high Jab1 expression was found to be associated with advanced clinicopathological features such as clinical stage, lymphatic metastasis, histological grade and distant metastasis in cancers. Our meta-analysis is the first to demonstrate that high Jab1 expression may be a promising indicator of poor prognosis and has an independent prognostic value for overall survival in patients with cancer.
Topics: Biomarkers, Tumor; COP9 Signalosome Complex; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Neoplasm Staging; Neoplasms; Peptide Hydrolases; Prognosis; Proportional Hazards Models; Publication Bias
PubMed: 33550701
DOI: 10.1111/jcmm.16334 -
Pathology, Research and Practice Nov 2021Numerous studies have examined the prognostic value of ubiquitin-specific protease 7 (USP7) in cancer, but the results remain controversial. Differences in assessment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have examined the prognostic value of ubiquitin-specific protease 7 (USP7) in cancer, but the results remain controversial. Differences in assessment assays (mRNA/protein) used could be a potential confounding factor. Thus, we extracted studies that measured the protein expression and performed a meta-analysis to assess the prognostic role of USP7 expression in cancer and to identify clinicopathological features associated with USP7 expression.
METHODS
PubMed, Scopus, Web of Science Core Collection, Wiley Online Library, and Google Scholar were searched from inception to July 2020. Pooled hazard ratios were calculated to evaluate the association between USP7 expression and overall survival (OS). In addition, pooled odds ratios were calculated to identify clinicopathological features associated with USP7 expression.
RESULTS
Eight studies in China were included in our meta-analysis, which had a total of 1192 patients and assessed five types of cancer. The pooled results revealed that a high expression of USP7 was associated with poor OS, especially in epithelial ovarian cancer (EOC). Moreover, USP7 expression was increased in patients with tumour-node-metastasis (TNM) stages III-IV, poor pathological grade, and positive lymph node metastasis. For patients with EOC, a high USP7 expression positively correlated with lymph node metastasis.
CONCLUSION
A high USP7 expression may promote cancer progression and predict unfavourable prognosis of cancer patients, especially those with EOC. Our findings suggest that USP7 inhibitors might be promising therapeutics for cancer patients with such characteristics.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Enzyme Inhibitors; Female; Humans; Lymphatic Metastasis; Molecular Targeted Therapy; Neoplasm Staging; Ovarian Neoplasms; Risk Assessment; Risk Factors; Ubiquitin-Specific Peptidase 7; Up-Regulation
PubMed: 34562828
DOI: 10.1016/j.prp.2021.153621 -
BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
Lung Cancer (Amsterdam, Netherlands) Aug 2020The prognostic role of BRCA1 associated protein-1 (BAP1) expression in malignant pleural mesothelioma (MPM) is a matter of debate. We aimed to clarify whether MPM... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The prognostic role of BRCA1 associated protein-1 (BAP1) expression in malignant pleural mesothelioma (MPM) is a matter of debate. We aimed to clarify whether MPM patients with loss of BAP1 expression have better overall survival (OS) compared to BAP1 positive patients.
METHODS
BAP1 immunohistochemical staining of tumor samples from 60 MPM patients treated at our institution with first-line chemotherapy was evaluated. A systematic literature search was also performed. Only cohort studies that investigated BAP1 by immunohistochemistry (IHC) and reported hazard ratio (HR) values for OS obtained through multivariate analysis (or adjusted for histotype) were considered. A dataset comprising 638 MPM patients was added to our cohort and included in the meta-analysis.
RESULTS
In our cohort, 23 samples (38 %) were BAP1 positive/retained (≥1 %) and 37 samples (62 %) were BAP1 negative/loss. BAP1 loss was associated with epithelioid histotype (p 0.01). Median OS times were 14.8 months (95 % CI: 10.7-29.3) and 18.1 months (95 % CI: 11.2-25.8) for negative and positive BAP1 expression, respectively (p 0.2). At multivariate analysis, again no differences were observed among the two groups (p 0.81). Similarly, the meta-analysis consisting of 698 patients showed no difference in terms of OS according to BAP1 status (HR 1.11; 95 % CI, 0·76-1·61; p 0.60).
CONCLUSIONS
BAP1 expression is not an independent prognostic factor for MPM patients and it should not be considered without taking into account tumor histotype. Future studies should investigate its predictive role in patients treated with new emerging therapies such as immunotherapy.
Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Prognosis; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 32622302
DOI: 10.1016/j.lungcan.2020.06.024