scholarly journals Serum Exosomal miRNAs Are Associated with Active Pulmonary Tuberculosis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shamila D. Alipoor ◽  
Payam Tabarsi ◽  
Mohammad Varahram ◽  
Mehrnaz Movassaghi ◽  
Mehdi Kazempour Dizaji ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Roc Curve Analysis ◽  
Infection Level ◽  
Diagnostic Biomarkers ◽  
Active Pulmonary Tuberculosis ◽  
Diagnostic Potential ◽  
Exosomal Mirnas ◽  
Novel Biomarkers ◽  
Exosomal Mirna ◽  
Limited Accuracy

Introduction. Tuberculosis (TB) remains a major threat to human health. Due to the limited accuracy of the current TB diagnostic tests, it is critical to determine novel biomarkers for this disease. Circulating exosomes have been used as diagnostic biomarkers in various diseases. Objective of the Study. In this pilot study, we examined the expression of miRNAs as biomarker candidates for the diagnosis of TB infection. Methods. Serum-derived exosomes were isolated from TB patients and matched control subjects. The expression of miR-484, miR-425, and miR-96 was examined by RT-PCR methods. Results. The expression of miR-484, miR-425, and miR-96 were significantly increased in serum of TB patients which correlated with the TB infection level. A receiver operating characteristic (ROC) curve analysis showed the diagnostic potency of each individual serum exosomal miRNA with an area under the curve AUC=0.72 for miR-484 (p<0.05), 0.66 for miR-425 (p<0.05), and 0.62 for miR-96 (p<0.05). Conclusion. These results demonstrate that exosomal miRNAs have diagnostic potential in active tuberculosis. The diagnostic power may be improved when combined with conventional diagnostic markers.

Neurogranin as a Novel Biomarker in Alzheimer’s Disease

2020 ◽  
Author(s):  
Luisa Agnello ◽  
Caterina Maria Gambino ◽  
Bruna Lo Sasso ◽  
Giulia Bivona ◽  
Salvatore Milano ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Neurological Diseases ◽  
Area Under The Curve ◽  
Curve Analysis ◽  
Phosphorylated Tau ◽  
Roc Curve Analysis ◽  
Total Tau ◽  
Novel Biomarkers ◽  
Good Diagnostic Accuracy

Abstract Background In this study, we investigated the possible role of 2 novel biomarkers of synaptic damage, namely, neurogranin and α-synuclein, in Alzheimer disease (AD). Methods The study was performed in a cohort consisting of patients with AD and those without AD, including individuals with other neurological diseases. Cerebrospinal fluid (CSF) neurogranin and α-synuclein levels were measured by sensitive enzyme-linked immunosorbent assays (ELISAs). Results We found significantly increased levels of CSF neurogranin and α-synuclein in patients with AD than those without AD. Neurogranin was correlated with total tau (tTau) and phosphorylated tau (pTau), as well as with cognitive decline, in patients with AD. Receiver operating characteristic (ROC) curve analysis showed good diagnostic accuracy of neurogranin for AD at a cutoff point of 306 pg per mL with an area under the curve (AUC) of 0.872 and sensitivity and specificity of 84.2% and 78%, respectively. Conclusions Our findings support the use of CSF neurogranin as a biomarker of synapsis damage in patients with AD.

scholarly journals Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Zhang ◽  
Huihui Li ◽  
Ming Yuan ◽  
Dong Li ◽  
Chang Sun ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Pcr Analysis ◽  
Go Annotation ◽  
Qrt Pcr ◽  
Noninvasive Biomarker ◽  
Novel Biomarkers ◽  
Negative Controls ◽  
Exosomal Mirna

Background. A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis. Methods. Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs. Results. A total of 24 miRNAs showed differential levels of enrichment with P<0.05 and log2 fold change>1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively. Conclusion. Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

scholarly journals Evaluation of the Diagnostic Potential of a Plasma Exosomal miRNAs Panel for Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiajia Yang ◽  
Xuan Li ◽  
Shuchun Wei ◽  
Lei Peng ◽  
Huaiming Sang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Roc Curves ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Kaplan Meier ◽  
Diagnostic Potential ◽  
Training Stage ◽  
Exosomal Mirnas ◽  
Tumor Phenotype

PurposeGastric cancer (GC) is often difficult to diagnose early in the disease and remains one of the most frequently occurring malignancies. This investigation looks at the diagnostic potential of a specific plasma exosomal miRNAs panel for GC.MethodsThis study analyzed 216 individual peripheral blood samples. 2 GEO datasets were analyzed and two miRNAs were selected - plasma exosomal miR-195-5p and miR-211-5p. Quantitative reverse-transcriptase PCR (qRT–PCR) was used to assess relative expressions and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficiency of miR-195-5p and miR-211-5p panel. The Kaplan-Meier method was used to assess the prognostic value of plasma exosomal miR-195-5p and miR-211-5p.ResultsGC patients possessed notably raised plasma levels of exosomal miR-195-5p and miR-211-5p. The area under ROC curves (AUCs) of miR-195-5p, miR-211-5p were 0.745, 0.798 in the screening phase and 0.762, 0.798 in the training stage respectively. GC was able to be diagnosed more accurately when both miRNAs were interpreted together (AUC=0.820 in the validation stage). Poorer prognosis was observed in GC patients who had plasma exosomal miR-195-5p and miR-211-5p of higher levels. In vitro experiments also confirmed that miR-195-5p and miR-211-5p is able to be transmitted between cells, and works to enhance tumor invasion, migration and proliferation while inhibiting cell apoptosis.ConclusionPlasma exosomal miR-195-5p and miR-211-5p may become potential biomarkers for GC diagnosis, and may be useful in predicting tumor phenotype.

scholarly journals Comprehensive Analysis of Peripheral Exosomal circRNAs in Large Artery Atherosclerotic Stroke

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Xiao ◽  
Ruihua Yin ◽  
Yuan Wang ◽  
Shaonan Yang ◽  
Aijun Ma ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Comprehensive Analysis ◽  
Circular Rnas ◽  
Large Artery ◽  
Rna Seq ◽  
Roc Curve Analysis ◽  
Qrt Pcr ◽  
Model Combining ◽  
Novel Biomarkers ◽  
The Individual

Exosomes are crucial vehicles in intercellular communication. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed (DE) exosomal circRNAs in five paired LAA and normal controls. Further, quantitative real-time PCR (qRT-PCR) was used to verify the RNA-Seq results in a cohort of stroke patients (32 versus 32). RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 DE circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs. Here, we show for the first time the comprehensive expression of exosomal circRNAs, which displayed the potential diagnostic and biological function in LAA stroke.

scholarly journals Platelet miRNA bio-signature discriminates between dementia with Lewy bodies and Alzheimer disease: A cross-sectional study.

2020 ◽  
Author(s):  
Ana Gámez-Valero ◽  
Jaume Campdelacreu ◽  
Dolores Vilas ◽  
Lourdes Ispierto ◽  
Daniela Samaniego ◽  
...  
Keyword(s):  
Roc Curve ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Area Under The Curve ◽  
Target Prediction ◽  
Cross Sectional Study ◽  
Roc Curve Analysis ◽  
Cross Sectional ◽  
Diagnostic Potential ◽  
Degenerative Dementia

Abstract Background Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets have been previously related to neurodegeneration. They contain microRNAs (miRNAs), and their analysis may provide disease biomarkers. Methods Small RNAs from platelets of DLB patients and controls were analyzed by Next Generation Sequencing (NGS), and miRNAs deregulated in DLB were selected. Expression of these miRNAs was then determined and validated by LNA-based qRT-PCR in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Their predictive diagnostic potential was calculated by ROC curve analysis. miRTarbase and miRGate were used for target prediction. Results We profiled the whole platelet miRNA transcriptome from 7 DLB patients and 7 controls using NGS. Twenty-two selected miRNAs were further validated in independent studies (2017–2019) including DLB (n = 59), AD (n = 28), and PD (n = 24) patients, and control individuals (n = 51). Our results demonstrated downregulated expression levels for hsa-let-7d-5p (fold change 0.14; p = 0.006), hsa-miR-132-5p (0.12; p = 0.0015), hsa-miR-142-3p (0.07; p = 0.00047), hsa-miR-146a-5p (0.07; p = 0.00035), hsa-miR-150-5p (0.10; p = 0.0098), hsa-miR-25-3p (0.13; p = 0.0019) and hsa-miR-26b-5p (0.09; p = 0.0014) in DLB compared to AD. ROC curve for this seven-miRNA biosignature yielded an area under the curve (AUC) of 1. Both hsa-miR-142-3p and hsa-miR-150-5p, were down-regulated in DLB compared to controls (AUC = 0.85). Comparing AD and controls, miRNAs hsa-miR-132-5p, hsa-miR-146a-5p, hsa-miR-25-3p, and hsa-miR-6747-3p were up-regulated in AD (AUC = 0.94); and hsa-miR-128-3p and hsa-miR-139-5p were down-regulated in PD compared to controls (AUC = 0.81). Predictive target analysis identified three disease-specific pathway clusters as a result of platelet-miRNA deregulation. In DLB, pathways related to gene expression and small RNA metabolism; in AD, pathways related to stress response and RNA stress granules; and in PD pathways related to protein phosphorylation, metabolism and degradation were identified. Conclusion A platelet-associated bio-signature composed of 7 miRNAs is highly specific and sensitive for distinguishing DLB from AD.

Differential microRNA expression in blood in multiple sclerosis

2013 ◽  
Vol 19 (14) ◽  
pp. 1849-1857 ◽  
Author(s):  
Helle Bach Søndergaard ◽  
Dan Hesse ◽  
Martin Krakauer ◽  
Per Soelberg Sørensen ◽  
Finn Sellebjerg
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Area Under The Curve ◽  
Magnetic Bead ◽  
Transcriptional Level ◽  
Diagnostic Biomarker ◽  
Roc Curve Analysis ◽  
Peripheral Blood Mononuclear ◽  
Altered Expression ◽  
Diagnostic Biomarkers

Background: microRNAs (miRNAs) regulate the expression of the genome at the post-transcriptional level. They play a role in autoimmunity and inflammation, and show potential for use as therapeutic targets in many diseases. With the recent detection of miRNAs in body fluids, the possibility for using miRNAs as diagnostic biomarkers has emerged. Objective: We assessed whether miRNAs contribute to the altered immune activation state in relapsing–remitting multiple sclerosis (RRMS) patients and investigated the possible use of miRNAs as diagnostic biomarkers in multiple sclerosis (MS). Methods: We performed global miRNA expression profiling analysis in peripheral blood mononuclear cells (PBMCs) and selected miRNAs were measured in plasma. We detected expression of miRNAs by real-time qPCR and compared results with cytokines related to inflammation and disease activity. Selected miRNAs were analyzed in PBMC subpopulations, after isolating them by magnetic bead separation. Results: We found that among validated miRNAs, let-7d correlated with the pro-inflammatory cytokine interleukin-1B. The miR-145 was 3-fold up-regulated in MS patients; its possible use as a diagnostic biomarker in PBMCs, plasma and serum was confirmed by ROC-curve analysis (Area under the curve (AUC) 0.785, p = 0.0004; 0.785, p = 0.004; 0.981, P < 0.0001, respectively). Conclusions: RRMS patients in remission had altered expression of miRNAs. We validated miR-145 as a potential diagnostic biomarker for the diagnosis of MS in blood, plasma and serum.

Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS

2021 ◽  
pp. jnnp-2021-327129
Author(s):  
Steffen Halbgebauer ◽  
Petra Steinacker ◽  
Federico Verde ◽  
Jochen Weishaupt ◽  
Patrick Oeckl ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Area Under The Curve ◽  
Characteristic Analysis ◽  
Neurofilament Light ◽  
Diagnostic Biomarkers ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
Auc Value ◽  
The Difference ◽  
Lateral Sclerosis

ObjectiveElevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential.MethodsIn total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer’s disease (n=20), Parkinson’s disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD).ResultsCSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94).ConclusionOur results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.

scholarly journals Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers

Bioimpacts ◽  
2021 ◽  
Author(s):  
Houman Kahroba ◽  
Nasser Samadi ◽  
Mostafa Mostafazadeh ◽  
Mohamad Saied Hejazi ◽  
Mohammad Reza Sadeghi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mirna Expression ◽  
Roc Curve ◽  
Mirna Expression Profile ◽  
Curve Analysis ◽  
Diagnostic Purpose ◽  
Roc Curve Analysis ◽  
Diagnostic Biomarkers ◽  
Diagnostic Potential ◽  
Serum Exosomes

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential. Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals. Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome. Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.

scholarly journals A Blood Exosomal miRNA Signature in Acute Respiratory Distress Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Gilles Parzibut ◽  
Monique Henket ◽  
Catherine Moermans ◽  
Ingrid Struman ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Cell Activation ◽  
Distress Syndrome ◽  
Immune Cell ◽  
Area Under The Curve ◽  
Small Rna Sequencing ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the high mortality associated with the disease. Despite a significant progress in the treatment of ARDS, our ability to identify early patients and predict outcomes remains limited. The development of novel biomarkers is crucial. In this study, we profiled microRNA (miRNA) expression of plasma-derived exosomes in ARDS disease by small RNA sequencing. Sequencing of 8 ARDS patients and 10 healthy subjects (HSs) allowed to identify 12 differentially expressed exosomal miRNAs (adjusted p &lt; 0.05). Pathway analysis of their predicted targets revealed enrichment in several biological processes in agreement with ARDS pathophysiology, such as inflammation, immune cell activation, and fibrosis. By quantitative RT-PCR, we validated the alteration of nine exosomal miRNAs in an independent cohort of 15 ARDS patients and 20 HSs, among which seven present high capability in discriminating ARDS patients from HSs (area under the curve &gt; 0.8) (miR-130a-3p, miR-221-3p, miR-24-3p, miR-98-3p, Let-7d-3p, miR-1273a, and miR-193a-5p). These findings highlight exosomal miRNA dysregulation in the plasma of ARDS patients which provide promising diagnostic biomarkers and open new perspectives for the development of therapeutics.

Serum exosomal miR-377-3p and miR-381-3p as diagnostic biomarkers in colorectal cancer

2021 ◽  
Author(s):  
Li Wang ◽  
Xingguo Song ◽  
Miao Yu ◽  
Limin Niu ◽  
Yajing Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Diagnostic Efficiency ◽  
Characteristic Analysis ◽  
Diagnostic Biomarkers ◽  
Transmission Electron ◽  
Healthy Donors ◽  
Exosomal Mirnas ◽  
Exosomal Mirna ◽  
Serum Exosomes

Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by qPCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC.

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