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Open Access Highly Accessed Research article

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

Yuhua Qi12, Lunbiao Cui2, Yiyue Ge2, Zhiyang Shi2, Kangchen Zhao2, Xiling Guo2, Dandan Yang2, Hao Yu2, Lan Cui2, Yunfeng Shan2, Minghao Zhou2, Hua Wang2 and Zuhong Lu1*

Author affiliations

1 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Si Pai Lou, Nanjing, 210096, China

2 Key Laboratories of Enteric Pathogenic Microbiology, Ministry of Health, Microbiological Laboratory, Jiangsu Center for Disease Prevention and Control (CDC), 172 Jiangsu Rd, Nanjing, 210009, China

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Citation and License

BMC Infectious Diseases 2012, 12:384  doi:10.1186/1471-2334-12-384

Published: 28 December 2012

Abstract

Background

Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection.

Methods

Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed.

Results

The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863.

Conclusions

Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

Keywords:
Tuberculosis; MicroRNA; Biomarker; Low-Density Array; qRT-PCR