Exploring the miRNome of extracellular vesicles in septic shock patients: diagnostic and prognostic biomarkers
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST1319 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-BSST1230 | biostudies-other
Project description:Septic shock represents a subset of sepsis with severe physiological aberrations and a higher mortality rate than sepsis alone. Currently, the laboratory tools which can be used to identify the state of septic shock are limited. In pre-clinical studies, extracellular vesicles (EVs), especially large EVs (lEVs), have been demonstrated a role as functional inflammatory mediators of sepsis. However, its longitudinal trend during the disease course has not been explored. In this study, the quantities and subtypes of plasma-derived lEVs were longitudinally compared between patients with septic shock (n = 21) and non-sepsis infection (n = 9), who presented within 48 h of their symptom onset. Blood specimens were collected for seven consecutive days after hospital admission. lEVs quantification and subtyping were performed using an imaging flow cytometer. The experiments revealed a higher lEVs concentration in septic shock patients than infected patients at the onset of the disease. In septic shock patients, lEVs concentration decreased over time as opposed to infected patients whose lEVs concentration is relatively static throughout the study period. The major contributors of lEVs in both septic shock and infected patients were of non-leukocyte origins; platelets, erythrocytes, and endothelial cells released approximately 40, 25, and 15% of lEVs, respectively. Among lEVs of leukocyte origins, neutrophils produced the highest number of EVs. Nevertheless, the proportion of each subtype of lEVs among the given amount of lEVs produced was similar between septic shock and infected patients. These findings raise the possibility of employing lEVs enumeration as a septic shock identifying tool, although larger studies with a more diverse group of participants are warranted to extrapolate the findings to a general population.
| S-EPMC8481381 | biostudies-literature
Project description:BackgroundHemorrhagic shock (HS) is responsible for approximately 2 million deaths per year worldwide and is caused in 80% by polytrauma. These patients need a precise and quick diagnostic, which should be based on a combination of laboratory markers and radiological data. Extracellular vesicles (EVs) were described as potential new markers and mediators in trauma. The aim of the present study was to analyze, whether the surface epitopes of plasma-EVs reflect HS in polytraumatized patients and whether cell-specific EV subpopulations are useful diagnostic tools.Material and methodsPlasma samples from polytraumatized patients (ISS ≥16) with HS (n=10) and without (n=15), were collected at emergency room (ER) and 24h after trauma. Plasma-EVs were isolated via size exclusion chromatography and EV-concentrations were detected by Coomassie Plus (Bradford) Assay. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with healthy controls (n=10). To investigate the diagnostic and prognostic potential of EVs subpopulations, results were correlated with clinical outcome parameters documented in the electronical patients' record.ResultsWe observed a significant reduction of the total amount of plasma EVs in polytrauma patients with HS, as compared to polytrauma patients without HS and healthy controls. We found significant reduction of CD42a+ and CD41b+ (platelet-derived) EVs in all polytrauma patients, as well as a reduction of CD29+ EVs compared to healthy volunteers (*p<0.05). CD44+ and CD31+ EVs were specifically altered in patients with HS (*p<0.05). Both EV populations showed a moderate correlation (r² = 0.42) with the transfusion of erythrocyte concentrate, were associated with non-survival and the need for catecholamines (*p<0.05).ConclusionOur data reveal that polytrauma patients with a hemorrhagic shock are characterized by a reduction of CD44+ and CD31+ plasma-EVs. Both EV populations showed a moderate correlation with the need of erythrocyte transfusion, were associated with non-survival and the need for catecholamines.
| S-EPMC10471799 | biostudies-literature
Project description:BackgroundSepsis is an inflammatory response caused by infection with pathogenic microorganisms. The body shock caused by it is called septic shock. In view of this, we aimed to identify potential diagnostic gene biomarkers of the disease.Material and methodsFirstly, mRNAs expression data sets of septic shock were retrieved and downloaded from the GEO (Gene Expression Omnibus) database for differential expression analysis. Functional enrichment analysis was then used to identify the biological function of DEmRNAs (differentially expressed mRNAs). Machine learning analysis was used to determine the diagnostic gene biomarkers for septic shock. Thirdly, RT-PCR (real-time polymerase chain reaction) verification was performed. Lastly, GSE65682 data set was utilized to further perform diagnostic and prognostic analysis of identified superlative diagnostic gene biomarkers.ResultsA total of 843 DEmRNAs, including 458 up-regulated and 385 down-regulated DEmRNAs were obtained in septic shock. 15 superlative diagnostic gene biomarkers (such as RAB13, KIF1B, CLEC5A, FCER1A, CACNA2D3, DUSP3, HMGN3, MGST1 and ARHGEF18) for septic shock were identified by machine learning analysis. RF (random forests), SVM (support vector machine) and DT (decision tree) models were used to construct classification models. The accuracy of the DT, SVM and RF models were very high. Interestingly, the RF model had the highest accuracy. It is worth mentioning that ARHGEF18 and FCER1A were related to survival. CACNA2D3 and DUSP3 participated in MAPK signaling pathway to regulate septic shock.ConclusionIdentified diagnostic gene biomarkers may be helpful in the diagnosis and therapy of patients with septic shock.
| S-EPMC8772133 | biostudies-literature
Project description:Most cancer-related deaths are caused by distant metastases, which are tumour cells that have escaped from a primary tumour and passed into the bloodstream to colonize a new organ. In this context, communication between tumour and stromal cells is essential. Indeed, tumor cells interact with cells in the tumor microenvironment and are able to modify them to their advantage. Both extracellular vesicles (EVs) and exosomes are heterogeneous populations of small vesicles present in the tumor microenvironment and in body fluids that have recently emerged as powerful mediators involved in this communication and their transport in fluids. Tumor cells release large quantities of exosomes containing tumor markers, which can then spread to distant locations.
The exosomes are of endosomal origin. They are composed of proteins, lipids, RNA and DNA, and they circulate in the bloodstream. They can be internalized by specific distant cells and thus deliver a functional message. It has recently been shown that tumor exosomes containing pro-metastatic factors form pre-metastatic niches, before the tumor cells actually arrive, while determining the metastatic organotropism of tumors. These properties are now opening up new avenues of research in tumor biomarkers. In recent years, several studies have highlighted different markers contained specifically in exosomes derived from cancer cells. Consequently, exosomes are considered as potential reservoirs of tumor biomarkers that could be clinically useful for the non-invasive diagnosis of cancer, with the advantage of being performed by liquid biopsy. The study of microRNA (miRNA) is of particular interest. Indeed, miRNAs are small non-coding RNAs (between 21 and 25 nucleotides) involved in the regulation of gene expression and which are frequently deregulated in cancer. Several studies underline that the variation of free miRNAs in the blood is correlated with the progression of the disease, particularly in colon cancer. However, the stability of free miRNAs is controversial. Therefore, exosomes represent a very advantageous means of transporting miRNAs in the blood, as they are able to protect miRNAs from degradation by RNAase.
The hypothesis of the project is that circulating exosomes derived from tumours contain markers including specific miRNAs that could be used as biomarkers of early prognosis (survival and progression), easily measured in blood samples from patients with colon cancer. But other molecules contained in exosomes could also be of interest.
| 2349603 | ecrin-mdr-crc
Project description:Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002⁻1.039, P = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.
| S-EPMC6407102 | biostudies-literature
Project description:Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality. Several candidate biomarkers including CX3CR1 and LILRB2 were identified as prognostic biomarkers.
2017-11-27 | GSE95233 | GEO
Project description:The microRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested as potential biomarkers in cancer diagnosis. This study was designed to evaluate the circulating sEV-derived miRNAs as biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC). We compared the miRNA profiles in plasma-derived sEVs between 16 patients with NPC and 5 healthy controls (HCs). A distinct set of miRNAs that were differentially expressed between patients with NPC and HCs was determined by means of integrative bioinformatics approaches. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that the target genes of the differentially expressed miRNAs (DEMs) were mainly involved in cancer-associated signaling pathways. Seven representative DEMs were selected and further validated in an additional 60 patients with NPC and 40 HCs using quantitative reverse-transcription PCR analysis (qRT-PCR). Receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of the sEV-miRNA-based model for diagnosis. The 3 miRNA-based model, comprising miR-134-5p, miR-205-5p, and miR-409-3p, showed good discriminating power with an area under the curve (AUC) value of 0.88 in the training set and 0.91 in the validation set. Furthermore, the diagnostic model had an excellent classification ability to distinguish patients with NPC at different clinical stages or Epstein-Barr virus infection status from HCs. In conclusion, our findings indicated that sEV-derived miRNA levels were altered in the plasma of patients with NPC in comparison with those in HCs. The model based on the 3 sEV-derived miRNAs could potentially act as an alternative or complementary approach for diagnosing NPC.
| S-EPMC8177774 | biostudies-literature
Project description:Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.
| S-EPMC8615485 | biostudies-literature
Project description:To evaluate the prevalence of myocardial dysfunction and its prognostic value in patients with severe sepsis and septic shock.Adult septic patients admitted to an intensive care unit were prospectively studied using transthoracic echocardiography within the first 48 hours after admission and thereafter on the 7th-10th days. Echocardiographic variables of biventricular function, including the E/e' ratio, were compared between survivors and non-survivors.A total of 99 echocardiograms (53 at admission and 46 between days 7 - 10) were performed on 53 patients with a mean age of 74 (SD 13) years. Systolic and diastolic dysfunction was present in 14 (26%) and 42 (83%) patients, respectively, and both types of dysfunction were present in 12 (23%) patients. The E/e' ratio, an index of diastolic dysfunction, was the best predictor of hospital mortality according to the area under the ROC curve (0.71) and was an independent predictor of outcome, as determined by multivariate analysis (OR = 1.36 [1.05 - 1.76], p = 0.02).In septic patients admitted to an intensive care unit, echocardiographic systolic dysfunction is not associated with increased mortality. In contrast, diastolic dysfunction is an independent predictor of outcome.
| S-EPMC4738818 | biostudies-other