title: Plasma microRNAs as biomarkers for myotonic dystrophy type 1.
abstract: Myotonic dystrophy type 1 (DM1) lacks non-invasive and easy to measure biomarkers, still largely relying on semi-quantitative tests for diagnostic and prognostic purposes. Muscle biopsies provide valuable data, but their use is limited by their invasiveness. microRNA (miRNAs) are small non-coding RNAs regulating gene expression that are also present in biological fluids and may serve as diseases biomarkers. Thus, we tested plasma miRNAs in the blood of 36 DM1 patients and 36 controls. First, a wide miRNA panel was profiled in a patient subset, followed by validation using all recruited subjects. We identified a signature of nine deregulated miRNAs in DM1 patients: eight miRNAs were increased (miR-133a, miR-193b, miR-191, miR-140-3p, miR-454, miR-574, miR-885-5p, miR-886-3p) and one (miR-27b) was decreased. Next, the levels of these miRNAs were used to calculate a "DM1-miRNAs score". We found that both miR-133a levels and DM1-miRNAs score discriminated DM1 from controls significantly and Receiver-Operator Characteristic curves displayed an area under the curve of 0.94 and 0.97, respectively. Interestingly, both miR-133a levels and DM1-miRNAs score displayed an inverse correlation with skeletal muscle strength and displayed higher values in more compromised patients. In conclusion, we identified a characteristic plasma miRNA signature of DM1. Although preliminary, this study indicates miRNAs as potential DM1 humoral biomarkers.
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Perfetti
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Greco
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy; University of Milan, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bugiardini
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cardani
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gaia
authors.affiliation: Goethe University, Frankfurt am Main, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy; University of Milan, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Meola
authors.affiliation: Policlinico San Donato-IRCCS, San Donato Milanese, Milan, Italy. Electronic address: fabio.martelli@grupposandonato.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000097:blood / Q000235:genetics*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarker; Myotonic dystrophy; Patients; Plasma; microRNA