Rational biomarker development for the early and minimally invasive monitoring of AML
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159028 | GEO | 2021/08/31
REPOSITORIES: GEO
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Project description:Rational biomarker development for the early and minimally invasive monitoring of AML
| PRJNA667439 | ENA
Project description:Recurrent disease remains the principal cause for treatment failure in acute myeloid leukemia (AML) across age groups. Reliable biomarkers of AML relapse risk and disease burden have been problematic, as symptoms appear late and current monitoring relies on invasive and cost-ineffective serial bone marrow (BM) surveillance. In this report, we discover a set of unique microRNA (miRNA) that circulates in AML-derived vesicles in the peripheral blood ahead of the general dissemination of leukemic blasts and symptomatic BM failure. Next-generation sequencing of extracellular vesicle-contained small RNA in 12 AML patients and 12 controls allowed us to identify a panel of differentially incorporated miRNA. Proof-of-concept studies using a murine model and patient-derived xenografts demonstrate the feasibility of developing miR-1246, as a potential minimally invasive AML biomarker.
| S-EPMC8579272 | biostudies-literature
Project description:Background: Renal cell carcinoma (RCC) accounts for about 2% of all cancers. Renal biopsy is the gold standard among the diagnostic tools, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for ccRCC detection are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, seems to be a general characteristic of malignant transformation. Consistently, cancer-derived EVs are enriched in the blood, urine and various malignant effusions of cancer patients. Therefore, urinary samples can be a non-invasive approach for discovering diagnostic biomarkers. Methods: We enrolled 33 clear-cell RCC (ccRCC) patients and 22 healthy subjects (HS), age and sex-matched, for urine collection and extracellular vesicles isolation by differential centrifugation. Transcriptional profiles of urinary EVs from 12 patients with ccRCC and 11 HS were generated using the Illumina HumanHT-12 v4 BeadChip oligonucleotide arrays. Microarray analysis led to the identification of RNA that were then validated using RT-qPCR. Results: We showed for the first time that urinary exosomal shuttle RNA (esRNA) was significantly different in ccRCC patients compared to HS and we identified three EVs esRNA involved in the tumor biology that are potentially suitable as non-invasive biomarkers. GSTA1, CEBPA and PCBD1 RNA levels decreased in urinary EVs of patients compared to HS. After 1 month post-operation, the levels of RNA increased to reach the normal level. Conclusions: This study suggests, for the first time, the potential use of the RNA content of urinary EVs to provide a non-invasive first step to diagnose the ccRCC. Total RNA obtained from urinary extracellular vesicles isolated from ccRCC patients and healthy subjects.
2016-09-01 | E-GEOD-72922 | biostudies-arrayexpress
Project description:Background: Renal cell carcinoma (RCC) accounts for about 2% of all cancers. Renal biopsy is the gold standard among the diagnostic tools, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for ccRCC detection are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, seems to be a general characteristic of malignant transformation. Consistently, cancer-derived EVs are enriched in the blood, urine and various malignant effusions of cancer patients. Therefore, urinary samples can be a non-invasive approach for discovering diagnostic biomarkers. Methods: We enrolled 33 clear-cell RCC (ccRCC) patients and 22 healthy subjects (HS), age and sex-matched, for urine collection and extracellular vesicles isolation by differential centrifugation. Transcriptional profiles of urinary EVs from 12 patients with ccRCC and 11 HS were generated using the Illumina HumanHT-12 v4 BeadChip oligonucleotide arrays. Microarray analysis led to the identification of RNA that were then validated using RT-qPCR. Results: We showed for the first time that urinary exosomal shuttle RNA (esRNA) was significantly different in ccRCC patients compared to HS and we identified three EVs esRNA involved in the tumor biology that are potentially suitable as non-invasive biomarkers. GSTA1, CEBPA and PCBD1 RNA levels decreased in urinary EVs of patients compared to HS. After 1 month post-operation, the levels of RNA increased to reach the normal level. Conclusions: This study suggests, for the first time, the potential use of the RNA content of urinary EVs to provide a non-invasive first step to diagnose the ccRCC.
2016-09-01 | GSE72922 | GEO
Project description:Relapse remains the major cause of mortality for patients with Acute Myeloid Leukemia (AML). Improved tracking of minimal residual disease (MRD) holds the promise of timely treatment adjustments to preempt relapse. Current surveillance techniques detect circulating blasts that coincide with advanced disease and poorly reflect MRD during early relapse. Here, we investigate exosomes as a minimally invasive platform for a microRNA (miRNA) biomarker. We identify a set of miRNA enriched in AML exosomes and track levels of circulating exosome miRNA that distinguish leukemic xenografts from both non-engrafted and human CD34+ controls. We develop biostatistical models that reveal circulating exosomal miRNA at low marrow tumor burden and before circulating blasts can be detected. Remarkably, both leukemic blasts and marrow stroma contribute to serum exosome miRNA. We propose development of serum exosome miRNA as a platform for a novel, sensitive compartment biomarker for prospective tracking and early detection of AML recurrence.
| S-EPMC4650871 | biostudies-literature
Project description:Implant-associated inflammation is a major cause for the reduced performance/lifetime and failure of numerous medical devices. Therefore, the ability to non-invasively and quantitatively monitor implant-associated inflammation is critically important. Here we show that implant-associated inflammation can be imaged via fluorescence imaging using near-infrared hydrocyanine dyes delivered either locally or intravenously in living mice. This imaging strategy allowed quantitative longitudinal monitoring of inflammation by detecting reactive oxygen species (ROS) released by inflammatory cells in response to implanted poly(ethylene terephthalate) (PET) disks or injected poly (lactic-co-glycolic acid) (PLGA) microparticles, and exhibited a strong correlation to conventional analysis of inflammation. Furthermore, modulation of inflammatory responses via controlled release of the anti-inflammatory agent dexamethasone was detected using this sensitive imaging approach. Thus, hydrocyanine-based fluorescence imaging of ROS could serve as a surrogate measure for monitoring implant-associated inflammation as well as evaluating the efficacy of therapeutic approaches to modulate host responses to implanted medical devices.
| S-EPMC3159805 | biostudies-literature
Project description:The conservation and management of wildlife requires the accurate assessment of wildlife population sizes. However, there is a lack of synthesis of research that compares methods used to estimate population size in the wild. Using a meta-analysis approach, we compared the number of detected individuals in a study made using live trapping and less invasive approaches, such as camera trapping and genetic identification. We scanned 668 papers related to these methods and identified data for 44 populations (all focused on mammals) wherein at least two methods (live trapping, camera trapping, genetic identification) were used. We used these data to quantify the difference in number of individuals detected using trapping and less invasive methods using a regression and used the residuals from each regression to evaluate potential drivers of these trends. We found that both trapping and less invasive methods (camera traps and genetic analyses) produced similar estimates overall, but less invasive methods tended to detect more individuals compared to trapping efforts (mean = 3.17 more individuals). We also found that the method by which camera data are analyzed can significantly alter estimates of population size, such that the inclusion of spatial information was related to larger population size estimates. Finally, we compared counts of individuals made using camera traps and genetic data and found that estimates were similar but that genetic approaches identified more individuals on average (mean = 9.07 individuals). Overall, our data suggest that all of the methods used in the studies we reviewed detected similar numbers of individuals. As live trapping can be more costly than less invasive methods and can pose more risk to animal well-fare, we suggest minimally invasive methods are preferable for population monitoring when less-invasive methods can be deployed efficiently.
| S-EPMC8702163 | biostudies-literature
Project description:Bladder cancer is one of the most common cancers. Since prognosis ameliorates with early detection, it is a challenge to develop techniques that could replace or complement the current diagnosis protocols. The study of extracellular vesicles (EVs) that are present in urine samples has become an attractive alternative. The present study describes the mRNA content of vesicles isolated from voided urine samples within bladder cancer context. To discover a genetic signature of cancer, RNA associated to EVs was analyzed by microarray technique. Total RNA isolated from Extracellular Vesicles obtained from urine of bladder cancer patients was compared with RNA isolated from urinary vesicles of non-cancer patients.
2014-01-29 | E-GEOD-51843 | biostudies-arrayexpress
Project description:In This work we analyzed the mirnome in plasma and corresponding extracellular vesicles (EVs) from 12 patients affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy aged matched controls. Using hierarchical clustering with the detection score microarrays provide for each miRNA and we identified a plasma signature of 19 miRNAs in all Rb cases that were able to discriminate both cases from controls.
2020-03-31 | GSE141208 | GEO
Project description:Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin-producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4(+) ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizone-fed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing-remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression.
| S-EPMC5006601 | biostudies-literature