ECE2018 Oral Communications MicroRNAs as biomarkers in endocrine diseases (5 abstracts)
Detecting blood micro-RNAs and proteins associated with Graves’ disease and orbitopathy
Filippo Biscarini 1 , Lei Zhang 2 , Giulia Masetti 2 , Danila Covelli 3 , Giuseppe Colucci 3 , Anja Eckstein 4 , U Kaiser 4 , Shazli Draman 2 , Ilaria Muller 2 , Luigi Lucini 5 , Marian Ludgate 2 & Mario Salvi 3
1Consiglio Nazionale Ricerche, Milan, Italy; 2Cardiff University, Cardiff, UK; 3University of Milan, Milan, Italy; 4University of Essen, Essen, Germany; 5Università Cattolica, Piacenza, Italy.
Graves’ Disease (GD) affects about 2% of the population in the UK, with female predominance. A proportion of GD patients (5–50%) develop orbitopathy (GO), which is characterized by tissue remodeling in the orbit leading to protrusion of the eye (proptosis). Blood biomarkers associated with GD or GO could be useful diagnostic or prognostic tools for researchers and clinicians. Within the framework of INDIGO IAPP-612116 (Investigation of Novel biomarkers and Definition of the role of the microbiome In Graves’ Orbitopathy) we aimed at seeking proteins and microRNA (miRNA) that could be markers of the development of GD and GO in patients from three European centers. Blood samples were collected from 33 patients (14 GD, 19 GO) and 13 healthy controls from Cardiff, Milan and Essen for miRNA and protein sequencing (Illumina’s HiSeq2000 and Agilent-6550 Funnel quadrupole-time-of-flight mass spectrometer). Euclidean distances based on miRNA and protein quantification were visualized through multidimensional scaling (MDS). The differential expression of miRNA and proteins among groups was analysed with multinomial regression models. Additionally, miRNA and proteins, both separately and together, were used to predict whether individuals belonged to the GD, GO or control groups. Lasso-penalised multinomial regression was used for predictions on 150 resampled datasets. This allowed the estimation, along with the accuracy of prediction, of the relative importance of specific miRNA and proteins. In total, 3025 miRNAs and 1886 proteins were detected. The MDS plot showed good separation of the three groups (GD, GO, controls). From 10-fold cross-validation, the accuracy of predictions was 0.71 or 0.81 with miRNA or protein data alone and 0.86 with miRNA and proteins combined. Comparable accuracy was measured within-group. Matching results from differential expression analysis and predictive models, 5 miRNA and 20 proteins have been identified as potential biomarkers. These include the novel miRNA Novel:19_15038, and the proteins Zonulin, Alpha-2 macroglobulin, Beta-2 glycoprotein 1 and Fibronectin. The functional analysis of miRNA targets and proteins identified relevant metabolic pathways, including hippo signaling pathway, bacterial invasion of epithelial cells, complement and coagulation cascades, longevity regulating pathway, mRNA surveillance pathway. Overall, results reveal differential expression of blood miRNA and proteins between GD and GO patients and healthy controls. Helpful biomarkers have been identified, which may be used for early diagnosis and prognosis of Graves disease, including the likelihood of its progression to orbitopathy, and represent a step forward in the direction of technology-driven precision medicine.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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