Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease.
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ABSTRACT:
SUBMITTER: Cortes-Serra N
PROVIDER: S-EPMC7392439 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chagas disease (CD) is emerging in nonendemic countries. Biomarkers for earlier therapeutic response assessment in chronic CD patients are much needed. Here, we describe the first proteomic profiling of plasma-derived extracellular vesicles from a heart-transplanted patient with chronic CD and show the potential of this approach for discovering such biomarkers.
2021-09-08 | PXD014668 | Pride
Project description:Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing a reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using a nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in the size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic Chagasic patients, particularly those with recurrent infection following an immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, the monitoring of treatment, and prognosis.
| S-EPMC10818975 | biostudies-literature
Project description:Breast cancer is the second cause of cancer-associated death among women and seriously endangers women's health. Therefore, early identification of breast cancer would be beneficial to women's health. At present, circular RNA (circRNA) not only exists in the extracellular vesicles (EVs) in plasma, but also presents distinct patterns under different physiological and pathological conditions. Therefore, we assume that circRNA could be used for early diagnosis of breast cancer. Here, we developed classifiers for breast cancer diagnosis that relied on 259 samples, including 144 breast cancer patients and 115 controls. In the discovery stage, we compared the genome-wide long RNA profiles of EVs in patients with breast cancer (n=14) and benign breast (n=6). To further verify its potential in early diagnosis of breast cancer, we prospectively collected plasma samples from 259 individuals before treatment, including 144 breast cancer patients and 115 controls. Finally, we developed and verified the predictive classifies based on their circRNA expression profiles of plasma EVs by using multiple machine learning models. By comparing their circRNA profiles, we found 439 circRNAs with significantly different levels between cancer patients and controls. Considering the cost and practicability of the test, we selected 20 candidate circRNAs with elevated levels and detected their levels by quantitative real-time polymerase chain reaction. In the training cohort, we found that BCExoC, a nine-circRNA combined classifier with SVM model, achieved the largest AUC of 0.83 [95% CI 0.77-0.88]. In the validation cohort, the predictive efficacy of the classifier achieved 0.80 [0.71-0.89]. Our work reveals the application prospect of circRNAs in plasma EVs as non-invasive liquid biopsies in the diagnosis and management of breast cancer.
| S-EPMC8660094 | biostudies-literature
Project description:In chronic lymphocytic leukemia (CLL) and very likely all cancer types, extracellular vesicles (EVs) are a common mechanism by which intercellular messages are communicated between normal, diseased, and transformed cells. Studies of EVs in CLL and other cancers have great variability and often lack reproducibility. For CLL patient plasma and cell lines, we sought to characterize current approaches used in isolating EV products and understand whether cell culture-conditioned media or complex biological fluids confound results. Utilizing nanoparticle tracking analysis, protein quantification, and electron microscopy, we show that ultracentrifugation with an OptiPrep cushion can effectively minimize contaminants from starting materials including plasma and conditioned media of CLL cell lines grown in EV-depleted complete RPMI media but not grown in the serum-free media AIM V commonly used in CLL experimental work. Moreover, we confirm the benefit of including 25 mM trehalose in PBS during EV isolation steps to reduce EV aggregation, to preserve function for downstream applications and characterization. Furthermore, we report the highest particles/μg EVs were obtained from our CLL cell lines utilizing the CELLine bioreactor flask. Finally, we optimized a proliferation assay that offers a functional evaluation of our EVs with minimal sample requirements.
| S-EPMC8410027 | biostudies-literature
Project description:Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16). Small-RNA-seq of RNA-pEVs was performed to identify differentially regulated small-RNAs (sRNAs) in EoE.Basal vs. controls and EoE.Basal vs. EoE.Post.tx comparisons. Candidate miRNAs were validated in an independent cohort (EoE patients, n=33; controls, n=14), and the diagnostic potential of miRNAs-pairs was assessed. Results: the pEVs-sRNA cargo differed among controls, EoE.Basal and EoE.Post.tx conditions. Compared with controls, Ser_Comb_22, Leu_Comb_5, miR-10b-5p and miR-125a-5 were upregulated in EoE.Basal, and miR-224-5p, miR-221-3p, let-7d-5p and miR-191-5p were downregulated. Combination of miR-221-3p and miR-10b-5p showed the best diagnostic performance in discovery (AUC=0.87) and validation (AUC=0.70) cohorts. Comparing EoE.Basal and EoE.Post.tx paired samples, miR-374a-5p and miR-30a-3p were upregulated in EoE.Basal, while miR-15a-5p and let-7d-5p were downregulated. Here, combination of mi-30a-3p and miR-15a-5p showed AUC values of 0.90 and 0.71 in discovery and validation cohorts respectively. MiR-30a-3p remained highly upregulated in EoE.Basal when compared to EoE.Post.tx in the validation cohort (p=0.001). Conclusions: The sRNA cargo of pEVs is related to the inflammatory activity in EoE. This study pioneers the use of pEVs as a non-invasive biomarker for EoE.
2024-10-15 | GSE275710 | GEO
Project description:Multiple myeloma (MM) is a hematological malignancy of clonal antibody-secreting plasma cells (PCs). MM diagnosis and risk stratification rely on bone marrow (BM) biopsy, an invasive procedure prone to sample bias. Liquid biopsies, such as extracellular vesicles (EV) in peripheral blood (PB), hold promise as new minimally invasive tools. Real-world studies analyzing patient-derived EV proteome are rare. Here, we characterized a small EV protein content from PB and BM samples in a cohort of 102 monoclonal gammopathies patients routinely followed in the clinic and 223 PB and 111 BM samples were included. We investigated whether EV protein and particle concentration could predict an MM patient prognosis. We found that a high EV protein/particle ratio, or EV cargo >0.6 µg/108 particles, is related to poorer survival and immune dysfunction. These results were supported at the protein level by mass spectrometry. We report a set of PB EV-proteins (PDIA3, C4BPA, BTN1A1, and TNFSF13) with a new biomarker potential for myeloma patient outcomes. The high proteomic similarity between PB and BM matched pairs supports the use of circulating EV as a counterpart of the BM EV proteome. Overall, we found that the EV protein content is related to patient outcomes, such as survival, immune dysfunction, and possibly treatment response.
| S-EPMC9254863 | biostudies-literature
Project description:Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases (CADs).
| S-EPMC4974341 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide, with lung adenocarcinoma (LUAD) being the most common histological subtype (approximately 40%). In the absence of reliable screening biomarkers for early diagnosis, most patients with LUAD are inevitably diagnosed at an advanced stage. MicroRNAs (miRNAs) encapsulated within plasma-derived extracellular vesicles (EVs) may be suitable for use as noninvasive diagnostic biomarkers for aggressive malignancies, including LUAD. In this study, we first investigated the miRNA profiles of plasma-derived EVs from LUAD patients and healthy donors, and then systematically evaluated the expression patterns of selected plasma-derived EV miRNAs in a large cohort of patients with LUAD and healthy controls. Notably, we observed that miR-451a, miR-194-5p, and miR-486-5p were significantly increased in EVs from LUAD patients, compared to healthy controls. The area under the curve values for the three miRNAs were 0.9040 (95% confidence interval [CI], 0.8633-0.9447) for miR-451a, 0.7492 (95% CI, 0.6992-0.7992) for miR-194-5p, and 0.9574 (95% CI, 0.9378-0.9769) for miR-486-5p, while the AUC of the combination of these three miRNAs was 0.9650. Thus, these results suggest that these EV miRNAs may be promising candidates for the development of highly effective, noninvasive biomarkers for early LUAD diagnosis.
| S-EPMC6886307 | biostudies-literature
Project description:tic disorders (TDs) are a series of childhood neuropsychiatric disorders characterized by invol-untary motor and/or vocal tics and commonly comorbid with several other psychopathological and/or behavioral disorders. In the present study, we aimed to identify serum small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the serum samples of children for Tic Disorders Diagnosis
2024-07-15 | GSE208318 | GEO
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