Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients
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AuthorPozo Agundo, Ana; Villaescusa, Nerea; Martorell Marugán, Jordi; Soriano, Olga; Leyva, Socorro; Jódar Reyes, Ana Belén; Botella, Luisa María; Carmona Sáez, Pedro; Blanco Encomienda, Francisco Javier
Hereditary hemorrhagic telangiectasiaLiquid biopsyExosomesmiRNAsArteriovenous malformations
Pozo-Agundo, A.; Villaescusa, N.; Martorell-Marugán, J.; Soriano, O.; Leyva, S.; Jódar-Reyes, A.B.; Botella, L.M.; Carmona-Sáez, P.; Blanco, F.J. Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients. Int. J. Mol. Sci. 2021, 22, 9450. https://doi.org/ 10.3390/ijms22179450
SponsorshipSpanish Program for Young Investigators of the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (grant number SAF2015- 74313JIN; MINECO/FEDER, UE); “Programa Operativo FEDER 2014–2020 and Consejería de Economía y Conocimiento de la Junta de Andalucía” (grant number B1-FQM-112-UGR18)
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 overrepresented 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.