Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis

Zhongqing Qian, Hui Liu, Musheng Li, Junchao Shi, Na Li, Yao Zhang, Xiaojie Zhang, Jingzhu Lv, Xueying Xie, Yunfei Bai, Qinyu Ge, Eun A. Ko, Haiyang Tang, Ting Wang, Xiaojing Wang, Zhaohua Wang, Tong Zhou, Wanjun Gu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Circular RNAs (circRNAs) are a class of novel RNAs with important biological functions, and aberrant expression of circRNAs has been implicated in human diseases. However, the feasibility of using blood circRNAs as disease biomarkers is largely unknown. Methods: We explored the potential of using human peripheral blood mononuclear cell (PBMC) circRNAs as marker molecules to diagnose active pulmonary tuberculosis (TB). Findings: First, we demonstrated that circRNAs are widely expressed in human PBMCs and that many are abundant enough to be detected. Second, we found that the magnitude of PBMC circRNAs in TB patients was higher than that in the paired healthy controls. Compared with host linear transcripts, the circRNAs within several pathways are disproportionately upregulated in active TB patients, including "Cytokine-cytokine receptor interaction", "Chemokine signaling pathway", "Neurotrophin signaling pathway", and "Bacterial invasion of epithelial cells". Based on the differentially expressed circRNAs within these pathways, we developed a PBMC circRNA-based molecular signature differentiating active TB patients from healthy controls. We validated the classification power of the PBMC circRNA signature in an independent cohort with the area under the receiver operating characteristic curve (AUC) at 0.946. Interpretation: Our results suggest that PBMC circRNAs are potentially reliable marker molecules in TB diagnosis.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Jan 1 2017

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Pulmonary Tuberculosis
Blood
Blood Cells
Tuberculosis
circular RNA
Cytokine Receptors
Molecules
Nerve Growth Factors
Biomarkers
Chemokines
ROC Curve
Area Under Curve
Epithelial Cells
RNA
Cytokines

Keywords

  • Biomarker
  • Circular RNA
  • PBMC
  • Tuberculosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis. / Qian, Zhongqing; Liu, Hui; Li, Musheng; Shi, Junchao; Li, Na; Zhang, Yao; Zhang, Xiaojie; Lv, Jingzhu; Xie, Xueying; Bai, Yunfei; Ge, Qinyu; Ko, Eun A.; Tang, Haiyang; Wang, Ting; Wang, Xiaojing; Wang, Zhaohua; Zhou, Tong; Gu, Wanjun.

In: EBioMedicine, 01.01.2017.

Research output: Contribution to journalArticle

Qian, Z, Liu, H, Li, M, Shi, J, Li, N, Zhang, Y, Zhang, X, Lv, J, Xie, X, Bai, Y, Ge, Q, Ko, EA, Tang, H, Wang, T, Wang, X, Wang, Z, Zhou, T & Gu, W 2017, 'Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis', EBioMedicine. https://doi.org/10.1016/j.ebiom.2017.12.007
Qian, Zhongqing ; Liu, Hui ; Li, Musheng ; Shi, Junchao ; Li, Na ; Zhang, Yao ; Zhang, Xiaojie ; Lv, Jingzhu ; Xie, Xueying ; Bai, Yunfei ; Ge, Qinyu ; Ko, Eun A. ; Tang, Haiyang ; Wang, Ting ; Wang, Xiaojing ; Wang, Zhaohua ; Zhou, Tong ; Gu, Wanjun. / Potential Diagnostic Power of Blood Circular RNA Expression in Active Pulmonary Tuberculosis. In: EBioMedicine. 2017.
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AU - Zhang, Yao

AU - Zhang, Xiaojie

AU - Lv, Jingzhu

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AU - Bai, Yunfei

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AU - Zhou, Tong

AU - Gu, Wanjun

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AB - Background: Circular RNAs (circRNAs) are a class of novel RNAs with important biological functions, and aberrant expression of circRNAs has been implicated in human diseases. However, the feasibility of using blood circRNAs as disease biomarkers is largely unknown. Methods: We explored the potential of using human peripheral blood mononuclear cell (PBMC) circRNAs as marker molecules to diagnose active pulmonary tuberculosis (TB). Findings: First, we demonstrated that circRNAs are widely expressed in human PBMCs and that many are abundant enough to be detected. Second, we found that the magnitude of PBMC circRNAs in TB patients was higher than that in the paired healthy controls. Compared with host linear transcripts, the circRNAs within several pathways are disproportionately upregulated in active TB patients, including "Cytokine-cytokine receptor interaction", "Chemokine signaling pathway", "Neurotrophin signaling pathway", and "Bacterial invasion of epithelial cells". Based on the differentially expressed circRNAs within these pathways, we developed a PBMC circRNA-based molecular signature differentiating active TB patients from healthy controls. We validated the classification power of the PBMC circRNA signature in an independent cohort with the area under the receiver operating characteristic curve (AUC) at 0.946. Interpretation: Our results suggest that PBMC circRNAs are potentially reliable marker molecules in TB diagnosis.

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