Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set ( = 23) as being able to stratify patients by risk of disease progression (log-rank = 0.00014; HR = 7.99, 95% CI 2.38-26.87). When challenged in a separate validation set ( = 24), it confirmed its ability to predict progression (log-rank = 0.00026; HR = 5.51, 95% CI 2.03-14.9). The value of our signature was also confirmed when overall survival was considered (log-rank = 0.0021, HR = 4.12, 95% CI 1.57-10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient's risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression.
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http://dx.doi.org/10.3390/cancers14174307 | DOI Listing |
BJS Open
December 2024
Institute of Cardiovascular Sciences, University College London, London, UK.
Background: While most thyroid nodules are benign, 7-15% are malignant. Patients with indeterminate thyroid nodules (specifically Bethesda IV/Thy3f) often undergo diagnostic hemithyroidectomy to reach a diagnosis on final histology. The aim of this study was to assess the feasibility of circulating large extracellular vesicles as diagnostic biomarkers in patients presenting with Thy3f thyroid nodules.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Xuanwu Hospital Capital Medical University, Beijing, Beijing, China.
Background: An urgent need exists for minimally invasive testing for accurate detection of Alzheimer's disease (AD). Circulating microRNAs (miRNAs) have been investigated as a promising candidate biomarker for AD diagnosis and prediction because of their involvement in multiple brain signaling pathways in both health and disease. This study developed and validated a serum miRNA panel in discriminating clinically diagnosed AD from age-matched cognitively healthy controls.
View Article and Find Full Text PDFBackground: This study introduces the Automated High-purity Exosome isolation-based AD diagnostics system (AHEADx). By analyzing and understanding the molecular cargo (proteins and miRNAs) carried by circulating exosomes, researchers found brain-derived exosome (BDE) levels of P-S396-tau, P-T181-tau, and Aβ1-42 are elevated up to 10 years prior to clinical symptoms. Currently, there is no available technology capable of simultaneously isolating and screening exosomal biomarkers for efficient and personalized precision medicine giving early AD diagnosis.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Latin American Institute for Brain Health (BrainLat), Universidad Adolfo Ibañez, Santiago, Chile.
Background: The content of circulating exosomes has been observed to be altered in response to changes in physiological and pathological conditions, and they are detectable in different human fluids such as blood. Studies focused on the quantification of Aβ and tau proteins, as molecules contained within exosomes, suggest that they are related with Alzheimer disease (AD) and frontotemporal dementia (FTD) development, demonstrated that plasma-derived exosome analysis is a good approach for searching for biomarkers in the development of dementia. Our aim is to identify new blood biomarkers to detect the AD or FTD in the Chilean population using machine learning based on exosomal miRNAs.
View Article and Find Full Text PDFDiabetes Obes Metab
January 2025
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, China.
Aims: This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).
Materials And Methods: This study employed a case-control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health.
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