Scientific RepoRtS | 7: 16751 | DOI:10.1038/s41598-017-17146-y
Screening and identication of
lncRNAs as potential biomarkers
for pulmonary tuberculosis
, Li-Liang Wei
, Li-Ying Shi
, Meng Li
, Ting-Ting Jiang
, Jing Chen
, Su Yang
, Hui-hui Tu
, Yu-ting Hu
, Lin Gan
, Lian-Gen Mao
, Chong Wang
& Ji-Cheng Li
Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and mortality
worldwide. Eective diagnostic methods for TB are lacking. In this study, we investigated long
non-coding RNAs (lncRNAs) in plasma using microarray and the potential diagnostic value of
lncRNAs for TB. We found a total of 163 up-regulated lncRNAs and 348 down-regulated lncRNAs.
Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-
expression (CNC) analyses showed that functions of dierentially expressed lncRNAs were mainly
enriched in the regulation of alpha-beta T cell activation and the T cell receptor signalling pathway.
Four dierentially expressed lncRNAs, NR_038221 (fold change = 3.79, P < 0.01), NR_003142 (fold
change = 1.69, P < 0.05), ENST00000570366 (fold change = 3.04, P < 0.05), and ENST00000422183
(fold change = 2.11, P < 0.001), were veried using RT-qPCR. Among those, NR_038221, NR_003142,
and ENST00000570366 were found to be up-regulated, while ENST00000422183 was down-regulated.
The value of the area under the curve (AUC) for the diagnostic model consisting of the four lncRNAs
was 0.845 (sensitivity = 79.2%, specicity = 75%). We further predicted 85 mRNAs and 404 miRNAs
that potentially interact with these lncRNAs. Our study revealed the potential value of lncRNAs as
biomarkers for early diagnosis of TB and the underlying mechanisms of these abnormally expressed
lncRNAs in the pathogenesis of TB.
Tuberculosis (TB) is a chronic pulmonary infection caused by Mycobacterium tuberculosis (MTB). It is one of
the ten diseases with the highest mortalities in the world. According to the World Health Organization (WHO)
report, there were an estimated 10.4 million new cases of TB and 1.4 million deaths due to TB in 2015 worldwide.
China ranks third among the high TB burden countries, with 0.92 million new cases of TB in 2015, accounting
for approximately 9% of the global incidence, and the death toll was approximately 35 thousand. China is also one
of the ve countries with the greatest burden of multidrug resistant (MDR)-TB
Accurate and early diagnosis is important for controlling infection and eective treatment of TB
. In China,
TB diagnosis is made by clinical manifestations, radiological and pathological changes, and acid-fast bacilli (AFB)
culture for Mycobacterium. However, the detection rate of AFB in newly infected TB patients is only 44% (15–20%
. e detection of MTB is the gold standard for diagnosis of TB. However, MTB culture takes 3–4
weeks, which may not be conducive to controlling the infection
. Although interferon gamma release assays
(IGRA) have been used to diagnose TB, great dierences between individuals have suggested that they are not
suitable for TB diagnosis
. erefore, eective methods for early diagnosis are imperative for preventing TB. Our
previous studies demonstrated the potential value of miRNAs and several proteins as biomarkers for early diag-
nosis of TB, and we also reported biomarkers for cured TB
In recent years, long non-coding RNAs (lncRNAs) have been shown to play important roles in many dis-
eases and have been demonstrated to be associated with many physiological and pathological processes, such as
embryonic development, immune responses, cardiovascular diseases and cancer
. Meanwhile, studies have
also shown that lncRNAs can serve as molecular biomarkers in the diagnosis and prognosis of many diseases,
Institute of Cell Biology, Zhejiang University, Hangzhou, 310058, P.R. China.
Department of Respiratory Medicine,
The Sixth Hospital of Shaoxing, Shaoxing, 312000, P.R. China.
Department of Clinical Laboratory, Zhejiang Hospital,
Hangzhou, 310013, P.R. China.
South China University of Technology School of Medicine, Guangzhou, 510006, P.R.
China. Correspondence and requests for materials should be addressed to J.-C.L. (email: email@example.com)
Received: 19 September 2017
Accepted: 22 November 2017
Published: xx xx xxxx