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

Abstract

BackgroundCircular 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.MethodsWe explored the potential of using human peripheral blood mononuclear cell (PBMC) circRNAs as marker molecules to diagnose active pulmonary tuberculosis (TB).FindingsFirst, 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.InterpretationOur results suggest that PBMC circRNAs are potentially reliable marker molecules in TB diagnosis.

Rat BodyMap transcriptomes reveal unique circular RNA features across tissue types and developmental stages

“…, testes (Liang et al 2017b), peripheral whole blood 62 (Memczak et al 2015), peripheral blood mononucleotide cells (Qian et al 2018), platelets 63 (Alhasan et al 2016), and exosomes (Li et al 2015a). CircRNAs have also been related to the 64 development of the fetal human brain (Szabo et al 2015), mouse brain (You et al 2015), fetal 65 porcine brain (Veno et al 2015), and Drosophila neural systems (Westholm et al 2014).…”

“…In addition, aberrant circRNA expression is related to 68 human diseases , including human cancers (Meng et al 2017), neural 69 degenerative diseases (Kumar et al 2017), hematological malignancies (Bonizzato et al 2016), 70 and infectious diseases (Qian et al 2018). However, these conclusions might be preliminary and premature, since the circRNA profiles 82 examined in these studies were derived from relatively small datasets, such as RNA sequencing 83…”

Signature of circular RNAs in peripheral blood mononuclear cells from patients with active tuberculosis

“…Of them, 145 circRNAs were elevated while only 26 circRNAs were reduced in TB samples compared with the controls, which were in line with the report that the circRNA's magnitude in PBMCs from active TB patients was significantly increased. 15 Moreover, our results showed that the expression pattern of circRNAs in PBMCs is similar to that in plasma, 16 where the most dysregulated circRNAs were enhanced upon Mtb infection. This indicates that circRNAs are possibly turned on to promote the pathogenesis and progression of To further address the feasibility of these verified circRNAs as potential biomarkers for active TB diagnosis, ROC curve was applied to evaluate their diagnostic value.…”

“…However, the three dysregulated circRNAs were not observed in the previous findings mentioned above. 13,15,21 This F I G U R E 4 Detailed presentation of interactions between hsa_circRNA_101128 and its five potential miRNA targets. The 2D structure displayed the MRE sequence, pairing of miRNA target nucleotides and seed type.…”

Expression Profile Analysis of Differentially Expressed Circular RNAs in Steroid-Induced Osteonecrosis of the Femoral Head

“…CircRNAs are reproducibly and easily detected in clinical blood samples. Stable and enriched circRNAs have been found in peripheral blood [19,20], as well as blood components, such as exosomes [21], plasma [22], platelets [23], erythrocytes [24], and mononuclear cells [25].…”