Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

Cell Physiol Biochem. 2018;45(3):1230-1240. doi: 10.1159/000487454. Epub 2018 Feb 9.


Background/aims: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB.

Methods: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy.

Results: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment.

Conclusion: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.

Keywords: Biomarkers; Circular RNAs; Microarray assay; Tuberculosis.

MeSH terms

  • Adult
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Pneumonia / diagnosis
  • Pneumonia / genetics
  • Pneumonia / metabolism
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Circular
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Transcriptome
  • Tuberculosis / diagnosis*
  • Tuberculosis / genetics
  • Tuberculosis / metabolism


  • Biomarkers
  • RNA, Circular
  • RNA