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PloS One 2016The value of Fas ligand (FASL) as a diagnostic immune marker for acute renal rejection is controversial; this meta-analysis aimed to clarify the role of FASL in acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The value of Fas ligand (FASL) as a diagnostic immune marker for acute renal rejection is controversial; this meta-analysis aimed to clarify the role of FASL in acute renal rejection.
METHODS
The relevant literature was included by systematic searching the MEDLINE, EMBASE, and Cochrane Library databases. Accuracy data for acute rejection (AR) and potential confounding variables (the year of publication, area, sample source, quantitative techniques, housekeeping genes, fluorescence staining, sample collection time post-renal transplantation, and clinical classification of AR) were extracted after carefully reviewing the studies. Data were analyzed by Meta-DiSc 1.4, RevMan 5.0, and the Midas module in Stata 11.0 software.
RESULTS
Twelve relevant studies involving 496 subjects were included. The overall pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio, together with the 95% CI were 0.64 (0.57-0.70), 0.90 (0.85-0.93), 5.66 (3.51-9.11), 0.30 (0.16-0.54), and 30.63 (14.67-63.92), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.9389. Fagan's nomogram showed that the probability of AR episodes in the kidney transplant recipient increased from 15% to 69% when FASL was positive, and was reduced to 4% when FASL was negative. No threshold effect, sensitivity analyses, meta-regression, and subgroup analyses based on the potential variables had a significant statistical change for heterogeneity.
CONCLUSIONS
Current evidence suggests the diagnostic potential for FASL mRNA detection as a reliable immune marker for AR in renal allograft recipients. Further large, multicenter, prospective studies are needed to validate the power of this test marker in the non-invasive diagnosis of AR after renal transplantation.
Topics: Biomarkers; Fas Ligand Protein; Graft Rejection; Granzymes; Humans; Kidney Transplantation; Perforin; Prognosis; RNA, Messenger; ROC Curve
PubMed: 27812144
DOI: 10.1371/journal.pone.0165628 -
Oncotarget Jan 2017Tetraspanin CD151, also known as PETA-3 or SFA-1, has been reported to predict prognosis in various solid tumors. Yet, the results of these studies remained... (Meta-Analysis)
Meta-Analysis Review
Tetraspanin CD151, also known as PETA-3 or SFA-1, has been reported to predict prognosis in various solid tumors. Yet, the results of these studies remained inconclusive. Here, we performed this meta-analysis of relevant studies published on the topic to quantitatively evaluate the clinicopathological significance of CD151 in solid tumors. The relevant articles were identified via searching the PubMed, Web of Science and Embase database. The pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) of overall survival (OS) and disease-free survival (DFS) were calculated to evaluate the prognostic value of CD151 expression in patients with solid tumors. A total of 19 studies involving 4, 270 participants were included in the study, we drew the conclusion that CD151 overexpression was associated with statistically significant poor OS (pooled HR = 1.498, 95% CI = 1.346-1.667, P<0.001) and poor DFS (pooled HR = 1.488, 95% CI = 1.314-1.685, P<0.001). Furthermore, the subgroup analysis revealed that the associations between CD151 overexpression and the outcome endpoints (OS or TTP) were significant within the Asian region and European, as well in patients with breast cancer or gastric cancer. Taken together, the incorporative HR showed CD151 overexpression was associated with poor survival in human solid tumors. CD151 could be a valuable prognosis biomarker or a potential therapeutic target of solid tumors.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Neoplasms; Prognosis; Tetraspanin 24
PubMed: 27888619
DOI: 10.18632/oncotarget.13532 -
Tumour Biology : the Journal of the... Jun 2017In the past decades, the oncogenic role of fibroblast growth factor receptor 2 has been demonstrated in a number of cancer types. However, studies have reported... (Meta-Analysis)
Meta-Analysis Review
In the past decades, the oncogenic role of fibroblast growth factor receptor 2 has been demonstrated in a number of cancer types. However, studies have reported contradictory findings concerning the correlation between fibroblast growth factor receptor 2 expression and prognosis in solid tumors. To address this discrepancy, we performed a meta-analysis with 18 published studies (2975 patients) retrieved from PubMed, EMBASE, and Web of science. Data were extracted and computed into odds ratios. The results showed that fibroblast growth factor receptor 2 overexpression was significantly associated with decreased 3-year overall survival (odds ratio = 1.93, 95% confidence interval: 1.30-2.85, p = 0.001) and 5-year overall survival (odds ratio = 1.62, 95% confidence interval: 1.07-2.44, p = 0.02) in patients with solid tumors. Subgroup analysis revealed that high fibroblast growth factor receptor 2 expression was also associated with poor prognosis of gastric cancer, hepatocellular carcinoma, and esophageal cancer, but not correlated with pancreatic cancer. In conclusion, fibroblast growth factor receptor 2 overexpression is correlated with decreased survival in most solid tumors, suggesting that the expression status of fibroblast growth factor receptor 2 is a valuable prognostic biomarker and a novel therapeutic target in human solid tumors.
Topics: Biomarkers, Tumor; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; PubMed; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 28618942
DOI: 10.1177/1010428317707424 -
International Journal of Clinical and... 2014CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC.
METHODS
Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated.
RESULTS
We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78].
CONCLUSION
Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Hyaluronan Receptors; Lung Neoplasms; Prognosis
PubMed: 25120740
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Mar 2020Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current...
OBJECTIVE
Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain.
CONCLUSIONS
Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.
Topics: Acetylation; Animals; Fibrinogen; Fibrinolysis; Glycosylation; Humans; Oxidation-Reduction; Polymerization; Protein Processing, Post-Translational; Thrombosis
PubMed: 31914791
DOI: 10.1161/ATVBAHA.119.313626 -
Current Cardiology Reviews 2017Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been gaining major attention recently after the emergence of data showing the promising role of these proteins... (Review)
Review
BACKGROUND
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been gaining major attention recently after the emergence of data showing the promising role of these proteins in lipid homeostasis and atherosclerosis process, glucose and blood pressure regulation.
MATERIALS AND METHODS
PubMed, EMBASE, Scholar and Scopus databases were searched to identify randomized controlled trials, observational studies, in-vitro trials and reviews about the role of PCSK9 in cardiovascular homeostasis.
RESULTS
PCSK9 was found to have major impact on lipid homeostasis and inflammatory process through regulation of low-density lipoprotein receptors. Furthermore, inflammation was found to stimulate the expression of PCSK9 in various cells. As for glomerular proteinuria, a positive correlation was determined between PCSK9 levels and the degree of proteinuria. Hypertension, a major cardiovascular risk factor, is likely affected by PCSK9 levels through their role on epithelial sodium channel (ENaC) surface expression. Likewise, some studies show that PCSK9 is associated with higher fasting blood glucose and plasma insulin, demonstrating a potential role of PCSK9 in glucose homeostasis. The role of PCSK9 in cardiovascular homeostasis is one that is still not completely unraveled.
CONCLUSION
Studies have clearly shown the implication of PCSK9 in the cardiovascular risk factors: the higher the PCSK9 levels, the higher the risk of atherosclerosis, fasting plasma glucose and insulin resistance. Inhibiting PCSK9 may therefore theoretically prove to present great benefits in diabetic patients with high cardiovascular risk.
Topics: Cardiovascular Diseases; Gene Expression Regulation; Homeostasis; Humans; Proprotein Convertase 9; Receptors, LDL
PubMed: 28782494
DOI: 10.2174/1573403X13666170804150954 -
Contrast Media & Molecular Imaging 2018Our purpose was to provide data regarding relationships between F-FDG PET and histopathological parameters in lung cancer. (Meta-Analysis)
Meta-Analysis
Standardized Uptake Values Derived from F-FDG PET May Predict Lung Cancer Microvessel Density and Expression of KI 67, VEGF, and HIF-1 but Not Expression of Cyclin D1, PCNA, EGFR, PD L1, and p53.
BACKGROUND
Our purpose was to provide data regarding relationships between F-FDG PET and histopathological parameters in lung cancer.
METHODS
MEDLINE library was screened for associations between PET parameters and histopathological features in lung cancer up to December 2017. Only papers containing correlation coefficients between PET parameters and histopathological findings were acquired for the analysis. Overall, 40 publications were identified.
RESULTS
Associations between SUV and KI 67 were reported in 23 studies (1362 patients). The pooled correlation coefficient was 0.44. In 2 studies (180 patients), relationships between SUV and expression of cyclin D1 were analyzed (pooled correlation coefficient = 0.05). Correlation between SUV and HIF-1 was investigated in 3 studies (288 patients), and the pooled correlation coefficient was 0.42. In 5 studies (310 patients), associations between SUV and MVD were investigated (pooled correlation coefficient = 0.54). In 6 studies (305 patients), relationships between SUV and p53 were analyzed (pooled correlation coefficient = 0.30). In 6 studies (415 patients), associations between SUV and VEGF expression were investigated (pooled correlation coefficient = 0.44). In 5 studies (202 patients), associations between SUV and PCNA were investigated (pooled correlation coefficient = 0.32). In 3 studies (718 patients), associations between SUV and expression of PD L1 were analyzed (pooled correlation coefficient = 0.36). Finally, in 5 studies (409 patients), associations between SUV and EGFR were investigated (pooled correlation coefficient = 0.38).
CONCLUSION
SUV may predict microvessel density and expression of VEGF, KI 67, and HIF-1 in lung cancer.
Topics: B7-H1 Antigen; Cyclin D1; Fluorodeoxyglucose F18; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Lung Neoplasms; Microvessels; Positron-Emission Tomography; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53
PubMed: 29983647
DOI: 10.1155/2018/9257929 -
International Journal of Molecular... Sep 2021Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension,...
Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding dysregulation and gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.
Topics: DNA Methylation; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epigenesis, Genetic; Humans; Methylenetetrahydrofolate Reductase (NADPH2); MicroRNAs; Promoter Regions, Genetic; RNA, Long Noncoding
PubMed: 34638838
DOI: 10.3390/ijms221910502 -
Asian Pacific Journal of Cancer... 2014The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU).
MATERIALS AND METHODS
A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias.
RESULTS
Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them.
CONCLUSIONS
This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinogenesis; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Peptic Ulcer; Polymorphism, Single Nucleotide; Stomach Neoplasms
PubMed: 24815441
DOI: 10.7314/apjcp.2014.15.7.3021 -
Frontiers in Immunology 2020The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of...
The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of signaling pathways involved in immune responses. Most TRIM proteins have E3 ubiquitin ligase activity, mediating polyubiquitination of target proteins. Emerging evidence demonstrates that TRIM proteins play important roles in innate immunity by regulating pattern recognition receptors, vital adaptor proteins, kinases, and transcription factors in innate immune signaling pathways. Additionally, the critical roles of TRIM proteins in adaptive immunity, especially in T cell development and activation, are increasingly appreciated. In this review, we aim to summarize the studies on TRIMs in both innate and adaptive immunity, focusing on their E3 ubiquitin ligase functions in pattern recognition receptor signaling pathways and T cell functions, shedding light on the developing new strategies for modulating innate and adaptive immune responses against invading pathogens and avoiding autoimmunity.
Topics: Adaptive Immunity; Animals; Humans; Immunity, Innate; Immunomodulation; Signal Transduction; T-Lymphocytes; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 33117334
DOI: 10.3389/fimmu.2020.02157