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CNS Neuroscience & Therapeutics Aug 2013Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and... (Review)
Review
Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and developing areas of the world. There is an urgent need for additional tools to guide treatment of TBI. The aim of this review is to establish the possible use of diagnostic TBI biomarkers in (1) identifying diffuse and focal brain injury and (2) assess their potential for determining outcome, intracranial pressure (ICP), and responses to therapy. At present, there is insufficient literature to support a role for diagnostic biomarkers in distinguishing focal and diffuse injury or for accurate determination of raised ICP. Presently, neurofilament (NF), S100β, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1) seemed to have the best potential as diagnostic biomarkers for distinguishing focal and diffuse injury, whereas C-tau, neuron-specific enolase (NSE), S100β, GFAP, and spectrin breakdown products (SBDPs) appear to be candidates for ICP reflective biomarkers. With the combinations of different pathophysiology related to each biomarker, a multibiomarker analysis seems to be effective and would likely increase diagnostic accuracy. There is limited research focusing on the differential diagnostic properties of biomarkers in TBI. This fact warrants the need for greater efforts to innovate sensitive and reliable biomarkers. We advocate awareness and inclusion of the differentiation of injury type and ICP elevation in further studies with brain injury biomarkers.
Topics: Animals; Biomarkers; Brain Injuries; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Spectrin; Ubiquitin Thiolesterase; tau Proteins
PubMed: 23710877
DOI: 10.1111/cns.12127 -
The American Journal of Emergency... Sep 2015Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker of traumatic brain injury (TBI). However, previous studies on levels of UCH-L1 in serum... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker of traumatic brain injury (TBI). However, previous studies on levels of UCH-L1 in serum remain inconsistent. This systematic review and meta-analysis were conducted on observational studies that reported the association between serum UCH-L1 levels and TBI.
METHODS
Studies were identified by searching PubMed and ISI Web of Science up to February 2015. For the continuous outcomes, we calculated the weighted mean difference and 95% confidence interval. The statistical analysis was performed by RevMan 5.1 and Stata 12 software. Only case-control studies were included if they had data on serum UCH-L1 levels in TBI patients and healthy controls. Funnel plot and Egger's regression test were applied to assess the potential publication bias.
RESULTS
Of the 145 selected studies, 11 observational studies (including 9 case-control and 2 case-crossover studies) met the selection criteria, containing a total of 1138 TBI cases and 1373 controls. Finally, 5 case-control studies (including 673 TBI and 1004 controls) were eligible for the present meta-analysis. The results of our study showed that there was a significant increase in serum UCH-L1 levels in patients with TBI compared to controls (weighted mean difference, 0.96; 95% confidence interval, 0.31-1.61; P = .004).
CONCLUSION
In conclusion, TBI cases had higher serum UCH-L1 concentrations than matched controls. This reinforces the conceptualization of UCH-L1 as a potential biomarker of TBI.
Topics: Biomarkers; Brain Injuries; Humans; Observational Studies as Topic; Prognosis; Ubiquitin Thiolesterase
PubMed: 26087705
DOI: 10.1016/j.ajem.2015.05.023 -
PloS One 2011As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized... (Review)
Review
As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family.
Topics: Databases, Protein; Deubiquitinating Enzyme CYLD; Dystroglycans; Genetic Predisposition to Disease; Genome-Wide Association Study; Hepatocyte Growth Factor; Humans; Inflammatory Bowel Diseases; Peptide Hydrolases; Protease Inhibitors; Proto-Oncogene Proteins; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Ubiquitin-Specific Proteases
PubMed: 21931648
DOI: 10.1371/journal.pone.0024106 -
Pituitary Aug 2019Cushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs).... (Meta-Analysis)
Meta-Analysis
PURPOSE
Cushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (~ 50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.
METHODS
DNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n = 630).
RESULTS
We identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p ≤ 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p < 0.1 × 10). Among the 5 series, the remission rates were higher in patients with USP8-mutated-alleles than in those with the USP8-WT-alleles (p < 0.1 × 10).
CONCLUSION
Our data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.
Topics: Alleles; Endopeptidases; Endosomal Sorting Complexes Required for Transport; Genetic Association Studies; Humans; Mutation; Pituitary ACTH Hypersecretion; Ubiquitin Thiolesterase
PubMed: 31273566
DOI: 10.1007/s11102-019-00973-9 -
Clinical Genetics Mar 2021Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3.... (Meta-Analysis)
Meta-Analysis
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a dominant neurodegenerative disease caused by the expansion of a CAG repeat tract in ATXN3. Anticipation and worsening of clinical picture in subsequent generations were repeatedly reported, but there is no indication that SCA3/MJD frequency is changing. Thus, we performed a systematic review and meta-analysis on phenomena with potential effect on SCA3/MJD recurrency in populations: instability of CAG repeat transmissions, anticipation, fitness, and segregation of alleles. Transmission of the mutant allele was associated with an increase of 1.23 CAG repeats in the next generation, and the average change in age at onset showed an anticipation of 7.75 years per generation; but biased recruitments cannot be ruled out. Affected SCA3/MJD individuals had 45% more children than related controls. Transmissions from SCA3/MJD carriers showed that the expanded allele was segregated in 64% of their children. In contrast, transmissions from normal subjects showed that the minor allele was segregated in 54%. The present meta-analysis concluded that there is a segregation distortion favoring the expanded allele, among children of carriers. Therefore, further studies on transmissions and anticipation phenomena as well as more observations about fertility are required to clarify these selective forces over SCA3/MJD.
Topics: Age of Onset; Alleles; Ataxin-3; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Heterozygote; Humans; Machado-Joseph Disease; Meiosis; Recurrence; Trinucleotide Repeat Expansion
PubMed: 33219521
DOI: 10.1111/cge.13888 -
Genes, Chromosomes & Cancer Oct 2016Biallelic inactivation of the tumor suppressor gene BRCA1-associated protein 1 (BAP1) has been demonstrated in several cancers, but its prognostic role has not been... (Meta-Analysis)
Meta-Analysis Review
Biallelic inactivation of the tumor suppressor gene BRCA1-associated protein 1 (BAP1) has been demonstrated in several cancers, but its prognostic role has not been completely explained. We aimed to investigate the risk associated with loss of BAP1 (BAP1-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS were searched from database inception until 09/15/2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of BAP1 (BAP1+) vs. BAP1- were included. Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to BAP1- adjusted for potential confounders. From 261 hits, 12 studies (including 13 cohorts) with 3,447 participants (BAP1-: n = 697; BAP1+: n = 2,750), with a median follow-up over 60 months, were meta-analyzed. Compared to BAP1+, BAP1- significantly increased all-cause mortality, cancer-specific mortality and risk of recurrence in all the tumor types analyzed, except for mesothelioma, in which the presence of BAP1 mutations correlates with a better prognosis. Furthermore, we demonstrated that BAP1 mutated colorectal and renal carcinomas are associated with high-tumor grading (P < 0.0001), and that BAP1 mutated is more common in women than in men (P < 0.0001). In conclusion, on the basis of our meta-analysis, we have demonstrated a peculiar role of BAP1 in influencing the prognosis in cancer. Thus, BAP1 could be considered as an important potential target for personalized medicine. © 2016 Wiley Periodicals, Inc.
Topics: Female; Genes, Tumor Suppressor; Humans; Male; Mutation; Neoplasm Recurrence, Local; Neoplasms; Prognosis; PubMed; Risk Factors; Tumor Suppressor Proteins; Ubiquitin Thiolesterase
PubMed: 27223342
DOI: 10.1002/gcc.22381 -
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 -
Genes, Chromosomes & Cancer May 2023Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of...
Clear cell mesothelioma is uncommon and shows predominance of clear cells with resemblance to clear cell carcinomas. Clinicopathologic and molecular descriptions of clear cell mesothelioma remained limited. In this study, we identified an index patient with clear cell mesothelioma, confirmed by immunohistochemical and ultrastructural studies. Targeted next-generation sequencing revealed the presence of an inactivating VHL mutation. We then systematically searched for VHL-mutant mesotheliomas in a comprehensive genomic profiling database of 1532 mesotheliomas. Collectively, we identified a cohort of four VHL-mutant clear cell mesotheliomas, including three peritoneal and one pleural tumors from three females and one male, with age range of 47-68 (median 63) years. Histologically, each tumor showed a microcystic to tubulopapillary architecture with prominent clear cells. By next-generation DNA sequencing, each of the four clear cell mesotheliomas harbored inactivating VHL mutations, while lacking other alterations typical of mesotheliomas such as BAP1, NF2, SETD2, CDKN2A, CDKN2B, TP53, and PTEN. By using low-pass whole genome sequencing on the index case and targeted next-generation sequencing on the remaining three cases, we identified extensive loss of heterozygosity throughout the genome but consistently sparing chromosomes 5, 7, and 20, characteristic of genomic near-haploidization. In summary, clear cell mesotheliomas were characterized by inactivating VHL mutations and genomic near-haploidization and appeared to represent a distinct clinicopathologic and molecular category of mesotheliomas. Our findings implicate VHL in the pathogenesis of a subset of mesotheliomas, particularly those with clear cell morphology.
Topics: Female; Male; Humans; Middle Aged; Aged; Haploidy; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mutation; Chromosome Aberrations; Genomics; Ubiquitin Thiolesterase; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 36515470
DOI: 10.1002/gcc.23119 -
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