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

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.KEYWORDS biomarker, leprosy, miRNA L eprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The infection affects primarily the skin and can cause damage to peripheral nerves, mucosa, and other organs, including liver and eyes. Leprosy is classified as a neglected tropical disease and remains one of the main causes of disability in the world (1-3). According to a World Health Organization (WHO) report including data from 138 countries, 211,974 newly diagnosed patients were notified in the year 2015 and 96% of them were reported from 22 countries, including Brazil (4).Leprosy presents a spectrum of clinical manifestations depending on the host immune response against M. leprae. It can be classified according to histopathological (Ridley-Jopling) criteria into different forms across two opposing poles: a so-called resistance pole responsible for a localized form of the disease (tuberculoid tuberculoid [TT]) and a susceptibility pole that is a disseminated form, which leads to the development of more severe clinical manifestations (lepromatous leprosy [LL]). There are also three intermediate and unstable forms: borderline tuberculoid (BT), borderline

Quantification of microRNA levels in plasma – Impact of preanalytical and analytical conditions

“…al. used single TaqMan assays to validate their findings from a TLDA-analysis, and found that the two methods were reproducible and comparable for 7 of the 16 microRNAs analyzed, and in agreement with our study they could not reproduce the TLDA findings for miR-92a in the qPCR analysis [ 24 ]. Other studies also found, that differences in microRNA levels between groups as detected by TLDA analyses, can only partly be reproduced in a validation cohort by the use of single TaqMan assays [ 25 – 27 ].…”

Differential Expression Profile of miR-27b, miR-29a, and miR-155 in Chronic Lymphocytic Leukemia and Breast Cancer Patients

“…26 The widespread overexpression of miR-27a in cancer has led to the belief that miR-27a is an oncogenic miRNA. 27 In the present study, miR-27a was upregulated in patients with metastases, suggesting that its upregulation was acquired in the course of tumor progression and during the acquisition of metastatic potential. Several studies have revealed the prognostic significance of miR-27a overexpression in various carcinomas, such as gastric cancer, 28 acute lymphoblastic leukemia, 29 and osteosarcoma.…”

“…Both the univariate analyses and multivariate ana-lyses indicated that miR-27a expression was an independent prognostic factor for BC progression. 27 Anti-apoptosis functions of miR-29a in BC cells have been reported by Choghaei et al 32 These controversial results of miR-29a in tumors indicated that based on the cancer type, miR-29a played different roles. In our study, we found that miR-29a was significantly upregulated in BC as compared with normal tissues, indicating that miR-29a was implicated in the progression of BC.…”

Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT

“…Due to their presence in the bodily fluids, exosomes are considered candidate biomarkers. The use of a combination of miRNAs as biomarkers, instead of one unique miRNA, has been considered to be a more powerful tool due to the possible overlap in miRNA targeting [ 49 ]. A miRNA may dampen or amplify a signal by participating in a negative or positive feedback loop [ 50 ].…”