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Medicine Aug 2016Cancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer has become a major public concern all over the world and early diagnosis of cancer is of great benefit for treatment and prognosis. Several studies have investigated the association between abnormal circulating microRNA-126 (miR-126) expression and the risk of various cancers, but the results are inconsistent. Therefore, this meta-analysis was carried out to assess the potential diagnostic value of miR-126 for cancer.
METHODS
Relevant studies were searched from PubMed, Embase, and Web of Science and we calculated the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operator characteristic curve (AUC) to assess the diagnostic value of miR-126 for cancer detection.
RESULTS
A total of 745 cancer patients and 749 controls from 11 studies of 7 papers were included in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 68% (95% confidence interval [CI]: 60-75%), the specificity was 76% (95% CI: 65-85%), the PLR was 2.87 (95% CI: 1.96-4.21), the NLR was 0.42 (95% CI: 0.35-0.52), the DOR was 7 (95% CI: 4-11), and the AUC was 0.77 (95%CI: 0.73-0.80). Moreover, the sample type, cancer type, sample size, and quality score might be sources of heterogeneity.
CONCLUSION
This systematic review and meta-analysis suggests that miR-126 has great potential to be a noninvasive biomarker in the diagnosis of cancer. However, more well-designed studies with larger sample size on the diagnostic value of miR-126 for cancer are needed in the future.
Topics: Biomarkers, Tumor; Humans; MicroRNAs; Neoplasms
PubMed: 27583885
DOI: 10.1097/MD.0000000000004644 -
Bioscience Reports May 2022The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between microRNA-21 (miRNA-21) and pathogenesis of lung cancer is a considerable focus of research interest. However, to our knowledge, no in-depth meta-analyses based on existing evidence to ascertain the value of miRNA-21 in diagnosis and clinical prognosis of lung cancer have been documented.
METHODS
We comprehensively searched all the literature pertaining to 'miRNA-21' and 'lung cancer' from four databases from the period of inception of each database until May 2020. Using specific inclusion and exclusion criteria, the literature for inclusion was identified and the necessary data extracted.
RESULTS
In total, 46 articles were included in the meta-analysis, among which 31 focused on diagnostic value and 15 on prognostic value. Combined sensitivity (SEN) of miRNA-21 in diagnosis of lung cancer was 0.77 (95% confidence interval (CI): 0.72-0.81), specificity (SPE) was 0.86 (95% CI: 0.80-0.90), diagnostic odds ratio (DOR) was (95% CI: 12-33), and area under the SROC curve (AUC) was 0.87 (95% CI: 0.84-0.90). No significant correlations were observed between abnormal expression of miRNA-21 and gender, smoking habits, pathological type and clinical stage of lung cancer (P>0.05). In terms of overall survival (OS), univariate analysis (hazards ratio (HR) = 1.49, 95% CI: 1.22-1.82) revealed high expression of miRNA-21 as an influencing factor for lung cancer. MiRNA-21 was confirmed as an independent risk factor for poor prognosis in multivariate analysis (HR = 1.65, 95% CI: 1.24-2.19).
CONCLUSION
MiRNA-21 has potential clinical value in the diagnosis and prognosis of lung cancer and may serve as an effective diagnostic marker and therapeutic target in the future.
Topics: Biomarkers, Tumor; Humans; Lung Neoplasms; MicroRNAs; Prognosis; Proportional Hazards Models
PubMed: 35441676
DOI: 10.1042/BSR20211653 -
Brain Research Bulletin Mar 2023MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression... (Meta-Analysis)
Meta-Analysis Review
MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression in patients with amyotrophic lateral sclerosis (ALS). Clinical data also confirmed that miRNAs in these patients are inconsistent across studies. A comprehensive systematic review and meta-analysis of current studies can help recognize the important roles of miRNAs during ALS development. Therefore, we initially aimed to perform a systematic literature review on the muscle or serum miRNAs in patients with ALS and healthy individuals. Subsequently, we quantitatively summarized the clinical data of muscle or serum miRNA of patients with ALS and healthy individuals using a meta-analytical technique. 11 studies comprising 281 patients with ALS and 244 healthy control (HC) controls were identified from PubMed and Web of Science for meta-analysis. A systematic review revealed that miRNA levels are closely associated with the occurrence of ALS disease. The expression levels of the most relevant miRNAs were either increased or decreased. The random-effects meta-analysis indicated that the levels of miR-206, miR-133b, and miR-338-3p were significantly elevated in patients with ALS than in HC subjects. By contrast, there was no significant differences in the miR-133a levels between patients with ALS and HC subjects. Collectively, our outcomes demonstrated that serum miR-206, miR-133b, and miR-338-3p were significantly increased in patients with ALS. We speculated that the increased expression levels of miR-206, miR-133b and miR-338-3p are potential promising biomarkers for ALS.
Topics: Humans; MicroRNAs; Amyotrophic Lateral Sclerosis; Biomarkers
PubMed: 36681253
DOI: 10.1016/j.brainresbull.2023.01.005 -
Scientific Reports Sep 2023Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs... (Meta-Analysis)
Meta-Analysis
Current clinical tests for Parkinson's disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. As microRNAs (miRNAs) are promising biomarkers of various diseases, including PD, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of biofluid miRNAs in PD. All studies reporting data on miRNAs expression in PD patients compared to controls were included. Gene targets and significant pathways associated with miRNAs expressed in more than 3 biofluid studies with the same direction of change were analyzed using target prediction and enrichment analysis. A bivariate model was used to calculate sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. While miR-24-3p and miR-214-3p were the most reported miRNA (7 each), miR-331-5p was found to be consistently up regulated in 4 different biofluids. Importantly, miR-19b-3p, miR-24-3p, miR-146a-5p, and miR-221-3p were reported in multiple studies without conflicting directions of change in serum and bioinformatic analysis found the targets of these miRNAs to be associated with pathways important in PD pathology. Of the 102 studies from the systematic review, 15 studies reported sensitivity and specificity data on combinations of miRNAs and were pooled for meta-analysis. Studies (17) reporting sensitivity and specificity data on single microRNA were pooled in a separate meta-analysis. Meta-analysis of the combinations of miRNAs (15 studies) showed that biofluid miRNAs can discriminate between PD patients and controls with good diagnostic accuracy (sensitivity = 0.82, 95% CI 0.76-0.87; specificity = 0.80, 95% CI 0.74-0.84; AUC = 0.87, 95% CI 0.83-0.89). However, we found multiple studies included more males with PD than any other group therefore possibly introducing a sex-related selection bias. Overall, our study captures key miRNAs which may represent a point of focus for future studies and the development of diagnostic panels whilst also highlighting the importance of appropriate study design to develop representative biomarker panels for the diagnosis of PD.
Topics: Male; Humans; MicroRNAs; Parkinson Disease; Biomarkers; Sensitivity and Specificity
PubMed: 37770507
DOI: 10.1038/s41598-023-43096-9 -
Journal of Cerebral Blood Flow and... Jun 2022This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of...
This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of microRNA expression in the diagnosis and prognosis of ischaemic or haemorrhagic stroke. Electronic databases were searched from 1993 to October 2021, using key words relevant to concepts of stroke and microRNA. Studies that met specific inclusion and exclusion criteria were selected for data extraction. To minimise erroneous associations, findings were restricted to microRNAs reported to change in more than two independent studies. Of the papers assessed, 155 papers reported a change in microRNA expression observed in more than two independent studies. In ischaemic studies, two microRNAs were consistently differentially expressed in clinical samples (miR-29b & miR-146a) and four were altered in preclinical samples (miR-137, miR-146a, miR-181b & miR-223-3p). Across clinical and preclinical haemorrhagic studies, four microRNAs were downregulated consistently (miR-26a, miR-126, miR-146a & miR-155). Across included studies, miR-126 and miR-146a were the only two microRNAs to be differentially expressed in clinical and preclinical cohorts following ischaemic or haemorrhagic stroke. Further studies, employing larger populations with consistent methodologies, are required to validate the true clinical value of circulating microRNAs as biomarkers of ischaemic and haemorrhagic stroke.
Topics: Biomarkers; Circulating MicroRNA; Hemorrhagic Stroke; Humans; MicroRNAs; Stroke
PubMed: 35240874
DOI: 10.1177/0271678X221085090 -
Oncotarget Jan 2018Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that develops from Barrett's esophagus (BE), an intestinal metaplasia of the distal esophagus.... (Review)
Review
Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that develops from Barrett's esophagus (BE), an intestinal metaplasia of the distal esophagus. microRNAs (miRNAs), short non-coding regulatory RNAs, are frequently dysregulated in BE and are thought to play key roles in the onset of BE and its progression to EAC. miRNAs thus have potential diagnostic and prognostic value and are increasingly being used as cancer biomarkers. This review summarizes the current literature related to miRNAs that are dysregulated in BE within the context of Hedgehog, Notch, MAPK, NF kappa-B, Wnt and epithelial-mesenchymal transition (EMT) signaling which are thought to drive BE onset and progression. This comprehensive analysis of miRNAs and their associated signaling in the regulation of BE provides an overview of vital discoveries in this field and highlights gaps in our understanding of BE pathophysiology that warrant further investigation.
PubMed: 29487725
DOI: 10.18632/oncotarget.24145 -
Experimental Biology and Medicine... Jan 2020Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P < 0.001) was the most upregulated, while miR-1-5p (logOR 7.290; P < 0.001) was the most downregulated. Subgroup analysis confirmed 53 significantly dysregulated miRNAs (21 upregulated and 32 downregulated) in cardiac tissue, with miRNA-1-5p and miRNA-223-3p being the most upregulated and downregulated miRNAs, respectively. Additionally, miR-328 and miR-1-5p were highly blood-specific, and miR-133 was animal-specific. In the detection method sub-groups, miRNA-29b and miRNA-223-3p were differentially expressed consistently. Four miRNAs, including miRNA-223-3p, miRNA-21, miRNA-328, and miRNA-1-5p, were consistently dysregulated in both Asian and non-Asian. Results of sensitivity analysis showed that 47 out of 51 (92.16%) miRNAs were dysregulated consistently. Totally, 51 consistently dysregulated miRNAs associated with atrial fibrillation were confirmed in this study. Five important miRNAs, including miR-29b, miR-328, miR-1-5p, miR-21, and miR-223-3p may act as potential biomarkers for atrial fibrillation.
IMPACT STATEMENT
Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.
Topics: Animals; Atrial Fibrillation; Computational Biology; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; MicroRNAs; Up-Regulation
PubMed: 31766887
DOI: 10.1177/1535370219890303 -
Journal of Stroke and Cerebrovascular... Nov 2023Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings.
METHODS
We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index.
SUMMARY OF REVIEW
112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential.
CONCLUSIONS
Despite sampling time differences, circulating microRNAs (< 24 h) and proteins (< 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.
Topics: Humans; Hemorrhagic Stroke; Stroke; Biomarkers; Ischemic Stroke; Glial Fibrillary Acidic Protein; MicroRNAs; RNA, Untranslated
PubMed: 37778160
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107388 -
International Journal of Molecular... Sep 2022The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge... (Review)
Review
The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge concerning the role of exosomes in CRS. For this systematic review, we searched PubMed/MEDLINE, Scopus, CENTRAL, and Web of Science databases for studies published until 7 August 2022. Only original research articles describing studies published in English were included. Reviews, book chapters, case studies, conference papers, and opinions were excluded. The quality of the evidence was assessed with the modified Office and Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies. Of 250 records identified, 17 were eligible, all of which had a low to moderate risk of overall bias. Presented findings indicate that exosomal biomarkers, including proteins and microRNA, act as promising biomarkers in the diagnostics and prognosis of CRS patients and, in addition, may contribute to finding novel therapeutic targets. Exosomes reflecting tissue proteomes are excellent, highly available material for studying proteomic alterations noninvasively. The first steps have already been taken, but more advanced research on nasal exosomes is needed, which might open a wider door for individualized medicine in CRS.
Topics: Animals; Biomarkers; Chronic Disease; Exosomes; Humans; MicroRNAs; Proteome; Proteomics; Rhinitis; Sinusitis
PubMed: 36232588
DOI: 10.3390/ijms231911284 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692