1. Identification of exosomal microrna signature by liquid biopsy in hereditary hemorrhagic telangiectasia patients
- Author
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Nerea Villaescusa, Olga Soriano, Socorro Leyva, Francisco J. Blanco, Ana Pozo-Agundo, Jordi Martorell-Marugán, Luisa María Botella, Ana Belén Jódar-Reyes, Pedro Carmona-Sáez, Ministerio de Economía y Competitividad (España), European Commission, Junta de Andalucía, Pozo-Agundo, Ana [0000-0003-2188-6296], Martorell-Marugán, Jordi [0000-0002-5186-0735], Soriano, Olga [0000-0001-7666-7969], Jodar, Ana-Belén [0000-0002-6136-7477], Botella, Luisa María [0000-0002-6310-2245], Carmona-Sáez, Pedro [0000-0002-6173-7255], Blanco, Francisco J. [0000-0003-2545-4319], Pozo-Agundo, Ana, Martorell-Marugán, Jordi, Soriano, Olga, Jodar, Ana-Belén, Botella, Luisa María, Carmona-Sáez, Pedro, Blanco, Francisco J., [Pozo-Agundo,A, Villaescusa,N, Soriano,O, Blanco,FJ] Department of Biochemistry and Molecular Biology (III) and Inmunology, School of Medicine, University of Granada, Granada, Spain. [Pozo-Agundo,A, Blanco,FJ] Centre for Biomedical Research, Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada, Spain. [Martorell-Marugán,J, Carmona-Sáez,P] Bioinformatics Unit, Pfizer, Andalusian Government Centre of Genomics and Oncological Research (GENYO), University of Granada, Granada, Spain. [Martorell-Marugán,J, Carmona-Sáez,P] Department of Statistics and OR, University of Granada, Granada, Spain. [Leyva,S] San Cecilio Clinic Universitary Hospital, Granada, Spain. [Jódar-Reyes,AB] Biocolloid and Fluid Physics Group, Excellence Research Unit Modeling Nature (MNat), Department of Applied Physics, School of Sciences, University of Granada, Granada, Spain. [Botella,LM] Department of Molecular Biomedicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain. [Botella,LM] Centro de Investigación Biomédica en Red, CIBERER, Instituto de Salud Carlos III, Madrid, Spain., This work was funded by the Spanish Program for Young Investigators of the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (grant number SAF2015-74313JIN, MINECO/FEDER, UE) to FJB, and and 'Programa Operativo FEDER 2014–2020 and Consejería de Economía y Conocimiento de la Junta de Andalucía' (grant number B1-FQM-112-UGR18) to ABJR
- Subjects
Telangiectasia hemorrágica hereditaria ,Pathology ,Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings] ,Gene Expression ,Telangiectases ,Exosomes ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings] ,Exosomas ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Cohort Studies ,Arteriovenous malformations ,hemic and lymphatic diseases ,Biology (General) ,Telangiectasia ,Spectroscopy ,MicroARNs ,Endoglin ,General Medicine ,Computer Science Applications ,Chemistry ,Phenotype ,Hereditary hemorrhagic telangiectasia ,miRNAs ,Telangiectasia, Hereditary Hemorrhagic ,Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] ,Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings] ,medicine.symptom ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings] ,Genotype ,QH301-705.5 ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Transcription, Genetic::Transcriptome [Medical Subject Headings] ,Mucocutaneous zone ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings] ,Exosome ,Article ,Catalysis ,Inorganic Chemistry ,Antigens, CD ,Diseases::Cardiovascular Diseases::Vascular Diseases::Arteriovenous Malformations [Medical Subject Headings] ,microRNA ,otorhinolaryngologic diseases ,medicine ,Humans ,Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Hemorrhagic Disorders::Hemostatic Disorders::Telangiectasia, Hereditary Hemorrhagic [Medical Subject Headings] ,Physical and Theoretical Chemistry ,Liquid biopsy ,QD1-999 ,Molecular Biology ,Receiver operating characteristic ,business.industry ,Gene Expression Profiling ,Organic Chemistry ,medicine.disease ,Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings] ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,MicroRNAs ,Gene Expression Regulation ,Dysplasia ,Biopsia líquida ,Mutation ,Malformaciones arteriovenosas ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD [Medical Subject Headings] ,business ,Transcriptome - Abstract
15 p.-5 fig.-3 tab., Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. Here, we carried out a liquid biopsy by which we isolated total RNA from plasma exosome samples. A cohort of 15 HHT type 1 patients, 15 HHT type 2 patients, and 10 healthy relatives were analyzed. Upon gene expression data processing and normalization, a statistical analysis was performed to explore similarities in microRNA expression patterns among samples and detect differentially expressed microRNAs between HHT samples and the control group. We found a disease-associated molecular fingerprint of 35 miRNAs over-represented in HHT vs. controls, with eight being specific for HHT1 and 11 for HHT2; we also found 30 under-represented, including nine distinct for HHT1 and nine for HHT2. The analysis of the receiver operating characteristic (ROC) curves showed that eight miRNAs had good (AUC > 75%) or excellent (AUC > 90%) diagnosis value for HHT and even for type HHT1 and HHT2. In addition, we identified the cellular origin of these miRNAs among the cell types involved in the vascular malformations. Interestingly, we found that only some of them were incorporated into exosomes, which suggests a key functional role of these exosomal miRNAs in the pathophysiology of HHT., This work was funded by the Spanish Program for Young Investigators of the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (grant number SAF2015-74313JIN; MINECO/FEDER, UE) to FJB; and “Programa Operativo FEDER 2014–2020 and Consejería de Economía y Conocimiento de la Junta de Andalucía” (grant number B1-FQM-112-UGR18) to ABJR.
- Published
- 2021