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Journal of Cancer 2018A number of studies revealed that copy number amplification and overexpression (on mRNA or protein expression level) were associated with prognosis of diverse cancers,...
A number of studies revealed that copy number amplification and overexpression (on mRNA or protein expression level) were associated with prognosis of diverse cancers, however, the results were inconsistent among studies. So we conducted this systematic review and meta-analysis to investigate the prognostic values of amplification and overexpression in cancer patients. PubMed, Cochrane library, Embase, CNKI and WanFang database (last update by February 15, 2018) were searched for literatures. A total of 20 studies were included and 5 survival assessment parameters were measured in this study, which included overall survival (OS), progression free survival (PFS), recurrence free survival (RFS), cancer specific survival (CSS) and distant metastasis free survival (DMFS). Pooled analyses showed that amplification might predict poor OS (HR=1.59, 95% CI: 1.05-2.40, =0.027) rather than PFS (HR=1.49, 95% CI: 0.83-2.67, =0.177) and RFS (HR=0.982, 95% CI: 0.2376-4.059, =0.9801) in various cancers; overexpression significantly correlated with poor OS (HR=1.52, 95% CI: 1.05-2.20, =0.027), PFS (HR=1.20, 95% CI: 1.07-1.34, =0.001) and DMFS (HR=1.62, 95% CI: 1.09-2.40, =0.017) rather than RFS (HR=1.68, 95% CI: 0.81-3.50, =0.164) and CSS (HR=1.54, 95% CI: 0.74-3.18, =0.246). On the whole, these results indicated amplification and overexpression were associated with poor survival of patients with cancer, suggesting that might be an effective prognostic signature for cancer patients.
PubMed: 30026836
DOI: 10.7150/jca.24179 -
Journal of Clinical Neuroscience :... Nov 2022Vasospasm is a common complication following subarachnoid hemorrhage (SAH), causing increased ischemia and tissue injury, and is implicated as a major risk factor for... (Review)
Review
INTRODUCTION
Vasospasm is a common complication following subarachnoid hemorrhage (SAH), causing increased ischemia and tissue injury, and is implicated as a major risk factor for poor outcomes. The success of current treatments for vasospasm is limited, with limited efficacy and unclear clinical benefits. Exosomes, vesicles that carry small molecules such as miRNA, have been theorized as a potential vasospasm treatment. In this study, we aim to survey the current literature discussing the role of exosomes in the setting of SAH.
METHODS
Following PRISMA guidelines, we performed a scoping review evaluating the role of exosomes in the treatment of SAH. The search was conducted using PubMed and Scopus, and all original research papers studying exosomal profiles of SAH research subjects or SAH therapy were eligible for inclusion.
RESULTS
After screening and full text review, seven papers were selected for final inclusion. Of these, two studies analyzed the expression profile of endogenous exosomes after SAH. Four papers identified and characterized miRNA-based exosomal therapies to attenuate early brain injury (EBI) after SAH. One paper discussed the role of protein overexpression in exosome delivery of miRNA for EBI after SAH. Interestingly, all identified papers studying exosomal therapy demonstrated anti-apoptotic or anti-inflammatory effects of miRNA exosomes acting via the BDNF/TrkB/CREB or HDAC3/NF-κB pathways.
CONCLUSION
Identified studies demonstrate potential neuroprotective benefits of miRNA-based exosomal treatment of EBI and SAH. Findings warrant further research investigating the anti-inflammatory and anti-apoptotic role of exosomal miRNA delivery in SAH models, specifically targeting the common pathway identified by the authors.
Topics: Anti-Inflammatory Agents; Brain Injuries; Brain-Derived Neurotrophic Factor; Exosomes; Humans; MicroRNAs; NF-kappa B; Subarachnoid Hemorrhage
PubMed: 36084567
DOI: 10.1016/j.jocn.2022.08.025 -
Medicine Oct 2015Nuclear factor-kappaB (NF-κB) is a key inflammatory transcription factor expressed frequently in tumors. Numerous studies have investigated the correlation between... (Meta-Analysis)
Meta-Analysis Review
Nuclear factor-kappaB (NF-κB) is a key inflammatory transcription factor expressed frequently in tumors. Numerous studies have investigated the correlation between NF-κB expression and prognosis in solid tumors, but the conclusions are still in contradiction. Here, we conduct a meta-analysis to explore the overall association of NF-κB overexpression and survival in human solid tumors. Pubmed and EBSCO databases were searched for studies evaluating expression of NF-κB (as measured by immunohistochemistry) and overall survival (OS) and disease-free survival (DFS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3, 5, and 10 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided. Forty-four studies with a total of 4418 patients were included in this meta-analysis. NF-κB overexpression was associated with worse OS at 3 years (OR = 3.40, 95% confidence interval [CI] = 2.41-4.79, P < 0.00001), 5 years (OR = 2.72, 95% CI = 1.92-3.85, P < 0.00001), and 10 years (OR = 2.63, 95% CI = .34-5.16, P = 0.005) of solid tumors. Results for 3- and 5-year DFS were similar. NF-κB expression was associated with poor 3-year OS in both Tumor, Lymph Node, Metastasis stage I-II (OR = 9.11, 95% CI = 2.90-28.68, P = 0.0002) and III-IV (OR = 2.59, 95% CI = 1.61-4.15, P < 0.0001). There is no correlation between cellular localization of NF-kB overexpression and OS of solid tumors. Among the tumor types, NF-κB was associated with worse 3 year-OS of colorectal cancer (OR = 2.70, 95% CI = 1.64-4.46, P < 0.0001), esophageal carcinoma (OR = 6.00, 95% CI = 3.29-10.94, P < 0.0001) and worse 5 year-OS of colorectal cancer (OR = 2.72, 95% CI = 1.92-3.85, P < 0.00001), esophageal carcinoma (OR = 5.96, 95% CI = 3.48-10.18, P = 0.03), and nonsmall cell lung cancer (OR = 1.69, 95% CI = 1.20-2.38, P = 0.002). Expression of NF-κB is associated with worse survival in most solid tumors irrespective of NF-κB localization.
Topics: Biomarkers, Tumor; Carcinoma; Female; Humans; Male; NF-kappa B; Odds Ratio; Prognosis; Survival Analysis
PubMed: 26448015
DOI: 10.1097/MD.0000000000001687 -
Critical Reviews in Oncology/hematology Jul 2023Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The... (Meta-Analysis)
Meta-Analysis Review
Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms
PubMed: 37210016
DOI: 10.1016/j.critrevonc.2023.104021 -
PloS One 2014Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes. Many studies have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has evaluated the relationship between SK1 and various cancers.
METHODS
We retrieved relevant articles from the PubMed, EBSCO, ISI, and OVID databases. A pooled odds ratio (OR) was used to assess the associations between SK1 expression and cancer; hazard ratios (HR) were used for 5-year and overall survival. Review Manager 5.0 was used for the meta-analysis, and publication bias was evaluated with STATA 12.0 (Egger's test).
RESULTS
Thirty-four eligible studies (n=4,673 patients) were identified. SK1 positivity and high expression were significantly different between cancer, non-cancer, and benign tissues. SK1 mRNA and protein expression levels were elevated in the cancer tissues, compared with the normal tissues. SK1 positivity rates differed between various cancer types (lowest [27.3%] in estrogen receptor-positive breast cancer and highest [82.2%] in tongue squamous cell carcinoma). SK1 positivity and high expression were associated with 5-year survival; the HR was 1.86 (95% confidence interval [CI], 1.18-2.94) for breast cancer, 1.58 (1.08-2.31) for gastric cancer, and 2.68 (2.10-3.44) for other cancers; the total cancer HR was 2.21 (95% CI, 1.83-2.67; P < 0.00001). The overall survival HRs were 2.09 (95% CI, 1.35-3.22), 1.56 (1.08-2.25), and 2.62 (2.05-3.35) in breast, gastric, and other cancers, respectively. The total effect HR was 2.21 (95% CI, 1.83-2.66; P < 0.00001).
CONCLUSIONS
SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival. SK1 positivity rates vary tremendously among the cancer types. It is necessary to further explore whether SK1 might be a predictive biomarker of outcomes in cancer patients.
Topics: Biomarkers, Tumor; Enzyme Activation; Gene Expression; Humans; Neoplasms; Phosphotransferases (Alcohol Group Acceptor); Proportional Hazards Models; Publication Bias; RNA, Messenger
PubMed: 24587339
DOI: 10.1371/journal.pone.0090362 -
The International Journal of Biological... Mar 2023The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not... (Meta-Analysis)
Meta-Analysis Review
The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; = 0.004), and tumor stage (III-IV) (OR = 1.96; 95% CI = 1.24, 3.09; = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.
Topics: Humans; Prognosis; Lymphatic Metastasis; Progression-Free Survival; Proportional Hazards Models; Biomarkers, Tumor; Perilipin-2
PubMed: 36604990
DOI: 10.1177/03936155221147536 -
Ageing Research Reviews Aug 2023The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence.
METHODS
PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies.
RESULTS
In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p = 0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p = 0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥ 4 years (SMD =1.21 [0.37;2.06], p = 0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p = 0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p < 0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD).
CONCLUSION
The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.
Topics: Humans; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Lipocalin-2; Mixed Dementias
PubMed: 37330019
DOI: 10.1016/j.arr.2023.101984 -
Indian Journal of Dental Research :... 2017The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic... (Review)
Review
BACKGROUND
The distinguishing feature of cancer cells is their ability to proliferate indefinitely, which is in contrast to the restricted cell multiplication potential for somatic cells. A better understanding of this contrasting behavior was provided in the early 1990s with the discovery of a relationship between telomeres, telomerase, aging, and cancer. Telomeres (tandem repeat DNA sequence TTAGGG) are protective caps at the ends of human chromosomes. Normal human cells experience telomere shortening with each successive cell division. However, in tumor cells, an overexpression of telomerase confers limitless replicative potential to tumor cells by continuous elongation of telomeres. The objective of this review was to systematically assess the data available on telomerase expression in oral cancer, with special reference to its role in diagnosis, prognosis, and treatment.
MATERIALS AND METHODS
A systematic review of studies that investigated the telomerase expression in oral squamous cell carcinoma (OSCC) was registered with PROSPERO. Subsequent to registration, a predetermined search strategy in accordance with PRISMA guidelines was formulated, and a literature search was conducted using online databases along with hand searching.
RESULTS
Eighty-nine articles from PubMed, 83 from Scopus, 5 from BioMed Central, 43 from Google Scholar, and 2 from hand search were identified. A total of 21 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for the markers under study, type of sample used, study design/methodology, and statistical analysis. The studies were then grouped into three subheads depending on their implications in the diagnosis, prognosis, and treatment of OSCC.
CONCLUSION
This review explains the basic biology and the clinical implications of telomerase-based diagnosis and prognosis, the prospects for its use in anticancer therapy, in the context of oral cancer.
Topics: Carcinoma, Squamous Cell; Cell Proliferation; Humans; Mouth Neoplasms; Prognosis; Telomerase; Telomere
PubMed: 29072223
DOI: 10.4103/ijdr.IJDR_690_16 -
Journal of Gastroenterology and... Jun 2021The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC.
METHODS
A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model.
RESULTS
Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC.
CONCLUSION
Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.
Topics: Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Hepatocellular; Female; Gene Expression; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Male; Prognosis; Survival Rate
PubMed: 33393670
DOI: 10.1111/jgh.15395 -
Obesity Reviews : An Official Journal... Jun 2017This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we... (Review)
Review
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression. Therefore, supplementation with ursolic acid may be an adjunctive therapy for prevention and treatment of obesity-mediated and muscle mass-mediated metabolic consequences.
Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Disease Models, Animal; Energy Metabolism; Humans; Muscle, Skeletal; Obesity; Thermogenesis; Transcription Factors; Triterpenes; Uncoupling Protein 1; Ursolic Acid
PubMed: 28335087
DOI: 10.1111/obr.12523