Characterization of MicroRNA Expression Profiles and Identification of Potential Biomarkers in Leprosy

Author:

Jorge Karina T. O. S.1,Souza Renan P.1,Assis Marieta T. A.1,Araújo Marcelo G.2,Locati Massimo3,Jesus Amélia M. R.4,Dias Baptista Ida M. F.5,Lima Cristiano X.6,Teixeira Antônio L.2,Teixeira Mauro M.7,Soriani Frederico M.1

Affiliation:

1. Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Minas Gerais, Brazil

2. Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil

3. Humanitas Clinical and Research Center, University of Milan, Milan, Italy

4. Departamento de Medicina Interna e Patologia, Universidade Federal de Sergipe, Sergipe, Brazil

5. Instituto Lauro de Souza Lima, São Paulo, Brazil

6. Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil

7. Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil

Abstract

ABSTRACT Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.

Funder

MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Publisher

American Society for Microbiology

Subject

Microbiology (medical)

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3. World Health Organization. 2016. Leprosy fact sheet (updated February 2017). World Health Organization, Geneva, Switzerland. http://www.who.int/mediacentre/factsheets/fs101/en/.

4. Patient contact is the major determinant in incident leprosy: implications for future control;van Beers SM;Int J Lepr Other Mycobact Dis,1999

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