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Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal novel vulnerabilities with prognostic significance in acute myeloid leukemia

ABSTRACT: RNA extracted from CD34+ isolated from Acute Myeloid Leukemia patients at the diagnosis and co-cultured with extracellular vesicles from plasma of AML patients at the diagnosis. Gene expression profiling was analyzed on the nCounter system using the Human Metabolic Pathways Panel comparing the expression profiles of EV-treated CD34+ cells and control (vehicle) CD34+ cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245810 | GEO | 2024/10/29

REPOSITORIES: GEO

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Prognostic significance of copy-number alterations in multiple myeloma

Project description:Purpose Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. Methods We performed a genome-wide analysis of malignant plasma cells from 192 newly myeloma patients using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. Results Our analyses revealed deletions and amplifications in 98% of cases. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis while recurrent amplifications of chromosomes 5, 9, 11, 15 and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3) and del(12p13.31). When adjusted to the established prognostic variables ie t(4;14), and serum beta2-microglobulin (Sb2M), del(12p13.31) remained the most powerful independent marker (P <.0001; hazard ratio = 3.17) followed by Sb2M (P <.0001; hazard ratio = 2.78) and amp(5q31.3) (P =.0005; hazard ratio = 0.37). Cases with amp(5q31.3) alone and low Sb2M had an excellent prognosis (5-year overall survival = 87%) conversely cases with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sb2M had a very poor outcome (5-year overall survival = 20%). Moreover, integration of SNP mapping and gene expression identified CD27 as potential critical gene responsible for poor prognosis of del(12p) myeloma patients. Conclusion These findings demonstrate the power and accessibility of molecular karyotyping to identify novel strong independent prognostic markers: amp(5q31.3) and del(12p13.31) and to provide insights into putative pathways deregulated in sub classes of cancer patients. Keywords: Human chromosome copy-number alterations study 192 myeloma patients at diagnosis examined with 500K Set Affymetrix chips

2009-08-19 | E-GEOD-12896 | biostudies-arrayexpress

Data-Independent Acquisition Mass Spectrometry Identification of Serum-derived Extracellular Vesicle Proteomics for Gastric Adenocarcinoma

Project description:Timely diagnosis of gastric adenocarcinoma (GAC) can effectively prevent the deterioration of the disease and significantly improve the survival rate of patients. Currently, tumor markers used in clinical practice cannot meet the needs of patients, and it is urgent to develop biomarkers with high sensitivity and specificity to guide clinical diagnosis. In this study, serum samples from 33 patients with GAC and 19 healthy persons were collected. EVs were extracted by ultracentrifugation and EV protein expression profiles were obtained by DIA quantitative mass spectrometry. Multi-group differential protein expression analysis showed that 23 intersecting proteins had the same expression trend, among which 15 EV proteins were chosen as candidate biomarkers for GAC diagnosis. Afterward, a subset of 2 to 6 proteins was randomly selected as features for logistic regression modeling. To verify the diagnostic performance of these models, serums from a new cohort of 12 patients with gastric cancer and 18 healthy controls were collected, and the EV protein were quantified using the same method. We finally found a panel consisting of six proteins that performed the best as classifier. We also tried to discover biomarkers for diagnosis of advanced stage in GAC, and the results showed a three-protein panel had the best classification performance. In conclusion, we identified new protein biomarker panels from serum EVs for early diagnosis of gastric cancer that worth further validation.

2023-03-11 | PXD027535 | Pride

Extracellular vesicle microRNA profiling in synovial fluids and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients: methodological challenges and identification of putative disease biomarkers

Project description:New early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic inflammatory arthritis in childhood and a leading cause of disability. Extracellular vesicles (EVs) released in the synovial fluid (SF) of inflamed joints have gained increased recognition as mediators of arthritis pathogenesis and as a source of biomarkers. No standardized protocol is available, yet, for the analysis of EV-derived microRNAs (EV-miRs) in human SF specimens, and their potential as biomarkers in OJIA has not been explored. This study proposes an optimized procedure for profiling EV-miRs in SF and represents the first investigation of the miRNome in EV isolated from OJIA patients at disease onset. We present data showing efficient recovery of EVs from SF aspirates and optimal profiling of their miRNA content. We identified a subset of 15 EV-miRs whose expression was deregulated in SF. Analysis of EV-miRs target genes evidenced the enrichemnt of processes related to inflammation, cartilage/bone homeostasis, hypoxia, and hormone metabolism, suggesting their contribution to disease pathogenesis and potential as new putative biomarkers. In addition, we detected altered expression levels of several circulating EV-miRs able to discriminate new-onset OJIA patients from control children. Among them, 16 were consensually overexpressed in both PL and SF from OJIA patients respect to controls, potentially representing a disease-associated molecular “fingerprint” measurable at both the systemic and local levels with high diagnostic potential. These results improve our understanding of OJIA molecular mechanisms and provide an important contribution in the search of new candidate biomarkers for early OJIA diagnosis and the design of novel tailored therapies.

2022-12-30 | GSE191326 | GEO

Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal novel vulnerabilities with prognostic significance in acute myeloid leukemia

Project description:Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal novel vulnerabilities with prognostic significance in acute myeloid leukemia

| PRJNA1030011 | ENA

Extracellular vesicles miR-574-5p and miR-181a-5p as prognostic markers in NSCLC patients treated with nivolumab

Project description:Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miR (miR-181a-5p, miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased mortality risk, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than six months. Grantee: Simona Coco Grantor: Italian Ministry of Health Grant ID: CO-2016-02361470 Grant Title: Exosomal miRNA signature as prognostic marker in advanced non-small cell lung cancer (NSCLC) patients treated with Nivolumab

2024-07-28 | GSE207715 | GEO

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer (microarray)

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by miRNA chip array, using Agilent-070156 Human_miRNA_V21.0_Microarray plateform. Results: Differential analysis showed the expressions of 27 EV delivered miRNAs were significantly different between serum of patients with bone-metastatic PCa and non-bone-metastatic PCa with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134266 | GEO

Deep sequencing identified serum extracellular vesicle delivered miR-181a-5p as an indicator for bone-metastatic prostate cancer

Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by deep sequencing, using Illumina HiSeqTM 2500 platform Results: Using an optimized data analysis method, we mapped about 17 million sequence reads per sample. Differential analysis showed the expressions of 35 EV delivered miRNAs were significantly different between serum of patients with PCa and BPH, with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.

2020-01-31 | GSE134205 | GEO

Extracellular vesicle long RNA markers of early-stage lung adenocarcinoma

Project description:The serum EV genes has great diagnostic value for lung adenocarcinoma patients with tumor size smaller than 2cm, which may serve as an important supplement to lung cancer screening.

2023-02-20 | GSE200288 | GEO

Real-time quantitative PCR analysis of microRNAs in CML stem cells

Project description:Lin-CD34+CD38+ and Lin-CD34-CD38- cells were isolated from 5 CML patients at diagnosis and 4 healthy donors.

2017-09-25 | GSE90773 | GEO

Evaluation of Novel Circulating Extracellular Vesicle-packaged microRNAs in Breast Cancer: a Potential Role for miR-128 and miRNA-27a

Project description:Purpose: Extracellular vesicle (EV)‑derived microRNAs (miRNAs) are a class of circulating miRNAs located in the plasma that are are now considered the next generation of cancer “theranostic” tools, with a strong clinical relevance. Although the potential role of EV-packaged miRNAs in breast cancer diagnosis has been widely reported, further studies are still demanded to address this challenging issue. The present study examined the expression profiles of EVs and circulating miRNAs with the aim of identifying novel miRNA signatures in breast cancer, and verify their diagnostic accurancy.

2023-12-06 | GSE239341 | GEO

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