Plasmatic exosome-derived circRNAs panel act as fingerprint for glioblastoma.
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ABSTRACT:
SUBMITTER: Xia D
PROVIDER: S-EPMC8386567 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionLack of diagnostic makers results in loss of operation opportunity in that most patients are diagnosed at the late stage. Pancreatic cancer (PC) has been regarded as a fatal disease with a 5-year survival rate below 10%. Therefore, the development of diagnostic biomarkers for PC is in urgent need to control the mortality of the disease.Materials and methodsThis is a case-control study including 640 plasma samples from healthy controls (HC), patients with benign pancreatic diseases (BPD), patients with PC; and patients with other gastrointestinal (GI) cancers. Eight biomarker candidates, including miR-20a, miR-21, miR-25, miR-155, miR-196a, miR-210, Macrophage Inhibitory Cytokine-1(MIC-1) and CA19-9, were evaluated to establish two diagnostic indexes in this study.ResultsThe plasma level of the six miRNAs and MIC-1, CA19-9 were elevated in PC patients compared with those of healthy controls (P<0.001). Among them, miR-20a, miR-21, miR-25, MIC-1 and CA19-9 could distinguish PC patients from those with other GI cancers or BPD. With multivariable logistic regression, we established two specific indexes for diagnosis of PC(Index1 contains miR-21, MIC-1 and CA19-9; Index2 contains miR-25, MIC-1 and CA19-9). In a randomized setting of 260 HC, 168 PC, 132 other GI cancers and 80 BPD patients, both indexes performed not only better sensitivity for PC but also better specificity to distinguish PC from other GI cancers than CA19-9 and individual biomarkers.ConclusionsThese results indicated that combination of biomarkers as a panel could improve diagnostic values compared with using a single marker. Such panels as illustrated in this study could provide novel plasmatic biomarker for PC diagnosis.
| S-EPMC5346769 | biostudies-literature
Project description:Background:Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. Methods:CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. Results:The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. Conclusions:We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.
| S-EPMC7546773 | biostudies-literature
Project description:Glioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness and resistance, as they carry and disseminate oncogenic material in the local tumor microenvironment and at distance. However, whether their quality and quantity reflect individual health status and changes in homeostasis is still not fully elucidated. Here, we separated EVs from plasma collected at different time points alongside with the clinical management of GBM patients. Our findings confirm that plasmatic EVs could be separated and characterized with standardized protocols, thereby ensuring the reliability of measuring vesiclemia, i.e. extracellular vesicle concentration in plasma. This unveils that vesiclemia is a dynamic parameter, which could be reflecting tumor burden and/or response to treatments. Further label-free liquid chromatography tandem mass spectrometry unmasks the von Willebrand Factor (VWF) as a selective protein hallmark for GBM-patient EVs. Our data thus support the notion that EVs from GBM patients showed differential protein cargos that can be further surveyed in circulating EVs, together with vesiclemia.
| S-EPMC8611030 | biostudies-literature
Project description:There is a urgent need for valuable strategy in early and less invasive diagnosis for cancer. Preliminary data have shown that the plasmatic levels of exosomes increase in cancer condition. This study investigates the relevance of plasmatic levels and size distribution of exosomes in 42 individuals with no signs of urological disease (CTR) as compared to 65 prostate cancer patients (PCa). It was used Nanoparticle Tracking Analysis (NTA), a highly reliable and sensitive method for exosomes characterization and quantification. The relation structure among the NTA-derived parameters was assessed by means of Principal Component Analysis, which allowed detecting the global discriminant power of NTA test in terms of Receiver Operating Characteristic (ROC) curve and the selection of cut-off thresholds. The results showed that PCa had significantly higher plasmatic levels of exosomes and that the exosomes were smaller in size as compared to the CTR; the values reached 89% sensitivity and 71% specificity, in distinguishing PCa from CTR. These results propose a new exosome-based non-invasive clinical approach for the clinical follow-up of prostate cancer undergoing surgical treatment; in addition this method may be developed as a new screening test for prostate cancer's early diagnosis. While this clinical study was performed in prostate cancer, it may represent a proof of concept extendable to virtually all cancers, as it is suggested by both pre-clinical evidence and clinical data obtained with different technical approaches.
| S-EPMC8564386 | biostudies-literature
Project description:Background Exosome circRNAs (Exo-circRNAs) regulate cancer progression and intercellular crosstalk in the tumor microenvironment. However, their biological functions and potential clinical importance in colorectal cancer (CRC) remain unknown. Methods We used exoRBase 2.0 data to identify significant differentially expressed Exo-circRNAs (Exo-DEcircRNAs) in CRC patients and healthy individuals. The least absolute shrinkage and selector operation algorithm, support vector machine-recursive feature elimination, and multivariate Cox regression analyses were used to select candidate Exo-circRNAs and constructed a diagnostic model. Quantitative reverse transcription-polymerase chain reaction analysis was performed to confirm the expression of Exo-circRNAs in the serum samples of patients. Furthermore, we constructed an exosome circRNA-miRNA-mRNA network for CRC. Upregulated target mRNAs in the exosome competing endogenous RNA (Exo-ceRNA) network were used for functional and pathway enrichment analyses. We identified 22 immune cell types in CRC patients using CIBERSORT. Correlation analysis revealed the relationship between Exo-ceRNA networks and immune-infiltrating cells. The relationship between target mRNAs and immunotherapeutic response was also explored. Finally, using the Kaplan–Meier survival curve, a prognostic upregulated target mRNA was screened. We constructed a survival-related Exo-ceRNA subnetwork and explored the correlation between the Exo-ceRNA subnetwork and immune-infiltrating cells. Results The constructed diagnostic model had a high area under the curve (AUC) value in both the training and validation sets (AUC = 0.744 and AUC = 0.741, respectively). qRT-PCR confirmed that the Exo-circRNAs were differentially expressed in CRC serum samples. We constructed Exo-ceRNA networks based on the interactions among seven upregulated Exo-DEcircRNAs, eight differentially expressed miRNAs, and twenty-two differentially expressed mRNAs in CRC. Functional enrichment analysis revealed that the upregulated target mRNAs were significantly enriched in cytoskeletal motor activity and the PI3K-Akt signaling pathway. Co-expression analysis showed a significant correlation between the Exo-ceRNA networks and immune cells. The significant correlation was observed between target mRNAs and the immunotherapeutic response. Additionally, based on the prognostic upregulated target gene (RGS2), we constructed a survival-related Exo-ceRNA subnetwork (Exosome hsa_circ_0050334-hsa_miR_182_5p-RGS2). CIBERSORT results revealed that the Exo-ceRNA subnetwork correlated with M2 macrophages (P = 4.6e-07, R = 0.31). Conclusions Our study identified an Exo-diagnostic model, established Exo-ceRNA networks, and explored the correlation between Exo-ceRNA networks and immune cell infiltration in CRC. These findings elucidated the biological functions of Exo-circRNAs and their potential clinical implications.
| S-EPMC9339618 | biostudies-literature
Project description:Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circRNA expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-contained circRNAs after AIS is still unknown. Plasma exosomes from ten AIS patients and ten controls were isolated, and through microarray and bioinformatics analysis, profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 FoldChange|≥1.00, P<0.05) between AIS patients and controls.The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion and leukocyte transendothelial migration, were associated with the development of AIS. As miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2- two RNA binding proteins (RBPs)- and play a role in AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls, and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.
2022-01-28 | GSE195442 | GEO
Project description:This research systematically profiled the global N6-methyladenosine modification pattern of circular RNAs (circRNAs) in glioblastoma (GBM). Based on RNA methylation sequencing (MeRIP sequencing or N6-methyladenosine sequencing) and RNA sequencing, we described the N6-methyladenosine modification status and gene expression of circRNAs in GBM and normal brain tissues. N6-methyladenosine-related circRNAs were immunoprecipitated and validated by real-time quantitative PCR. Bioinformatics analysis and related screening were carried out. Compared with those of the NC group, the circRNAs from GBM exhibited 1370 new N6-methyladenosine peaks and 1322 missing N6-methyladenosine peaks. Among the loci associated with altered N6-methyladenosine peaks, 1298 were up-regulated and 1905 were down-regulated. The N6-methyladenosine level tended to be positively correlated with circRNA expression. Bioinformatics analysis was used to predict the biological function of N6-methyladenosine-modified circRNAs and the corresponding signalling pathways. In addition, through PCR validation combined with clinical data mining, we identified five molecules of interest (BUB1, C1S, DTHD1, F13A1 and NDC80) that could be initial candidates for further study of the function and mechanism of N6-methyladenosine-mediated GBM development. In conclusion, our findings demonstrated the N6-methyladenosine modification pattern of circRNAs in human GBM, revealing the possible roles of N6-methyladenosine-mediated novel noncoding RNAs in the origin and progression of GBM.
| S-EPMC8335669 | biostudies-literature
Project description:MiRNAs represent a mechanism that regulates gene expression in many pathological conditions. Exosomes are known to be secreted from all types of cells, and the exosomes-released molecules are crucial messengers that can regulate cellular processes. We investigated the miRNAs content of exosomes released by cancer cells during the invasion . An invasion stimulus has been generated through scratches created on the confluent cells of cancer cell lines: glioblastoma, breast and prostate cancers.Several miRNAs were found to be significantly differentially abundant during the cell invasion , both in common among different cell lines and exclusive. Understanding the language codes among cells involved in invasion can lead to the development of therapies that can inhibit cellular communication, slowing or eventually stopping their activity.
| S-EPMC8224203 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent and spliced exons, are released in a circular form. CircRNAs are cell-type specifically expressed, are unusually stable, and can be found in various body fluids such as blood and saliva. Here we analysed circRNAs and the corresponding linear splice isoforms from human platelets, where circRNAs are particularly abundant, compared with other hematopoietic cell types. In addition, we isolated extracellular vesicles from purified and in vitro activated human platelets, using density-gradient centrifugation, followed by RNA-seq analysis for circRNA detection. We could demonstrate that circRNAs are packaged and released within both types of vesicles (microvesicles and exosomes) derived from platelets. Interestingly, we observed a selective release of circRNAs into the vesicles, suggesting a specific sorting mechanism. In sum, circRNAs represent yet another class of extracellular RNAs that circulate in the body and may be involved in signalling pathways. Since platelets are essential for central physiological processes such as haemostasis, wound healing, inflammation and cancer metastasis, these findings should greatly extend the potential of circRNAs as prognostic and diagnostic biomarkers.
| S-EPMC5769804 | biostudies-literature
Project description:PurposeGlioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient-derived xenografts (PDX) and undertaken its genomic and phenotypic characterization.Experimental designPDXs were established from glioblastoma, IDH-wildtype (n = 93), glioblastoma, IDH-mutant (n = 2), diffuse midline glioma, H3 K27M-mutant (n = 1), and both primary (n = 60) and recurrent (n = 34) tumors. Tumor growth rates, histopathology, and treatment response were characterized. Integrated molecular profiling was performed by whole-exome sequencing (WES, n = 83), RNA-sequencing (n = 68), and genome-wide methylation profiling (n = 76). WES data from 24 patient tumors was compared with derivative models.ResultsPDXs recapitulate many key phenotypic and molecular features of patient tumors. Orthotopic PDXs show characteristic tumor morphology and invasion patterns, but largely lack microvascular proliferation and necrosis. PDXs capture common and rare molecular drivers, including alterations of TERT, EGFR, PTEN, TP53, BRAF, and IDH1, most at frequencies comparable with human glioblastoma. However, PDGFRA amplification was absent. RNA-sequencing and genome-wide methylation profiling demonstrated broad representation of glioblastoma molecular subtypes. MGMT promoter methylation correlated with increased survival in response to temozolomide. WES of 24 matched patient tumors showed preservation of most genetic driver alterations, including EGFR amplification. However, in four patient-PDX pairs, driver alterations were gained or lost on engraftment, consistent with clonal selection.ConclusionsOur PDX panel captures the molecular heterogeneity of glioblastoma and recapitulates many salient genetic and phenotypic features. All models and genomic data are openly available to investigators.
| S-EPMC7056576 | biostudies-literature