Utility Of Plasma circBNC2 As A Diagnostic Biomarker In Epithelial Ovarian Cancer

BACKGROUND: Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in women. Due to a lacking of early detection method, its five-year survival rate is only 30%. Nevertheless, novel biomarkers for diagnosis remain to be discovered. The potential of microRNA signatures in the diagnosis of EOC has been especially described in recent years. In our previous experiments, we identified that circBNC2 was downregulated in EOC specimens, and was associated with advanced tumor stage and lymph node metastasis (LNM) by performing circRNA-sequencing analysis. The aim of this study was to explore the diagnostic value of circBNC2 in patients with epithelial ovarian cancer (EOC). METHODS: Plasma from 249 age and menopause-matched women (83 with EOC; 83 with benign ovarian cyst; 83 were healthy volunteers) was collected prior to surgery. CircBNC2 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were analyzed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated. RESULTS: CircBNC2 was downregulated in EOC and had higher ROC AUC in comparing EOC to benign (ROC AUC 0.879, sensitivity 96.4%, specificity 80.7%) or healthy (ROC AUC 0.923, sensitivity 95.2%, specificity 85.5%) cohorts than HE4 (ROC AUC: 0.742, benign cohort; 0.779, healthy cohort) and CA125 (ROC AUC: 0.373, benign cohort; 0.713, healthy cohort). Early stage EOC vs benign (ROC AUC 0.864, sensitivity 92.0%, specificity 80.7%) and healthy (ROC AUC 0.908, sensitivity 92.0%, specificity 85.5%) cohorts could be significantly separated by circBNC2. CircBNC2 performed alike in pre- and postmenopausal women, within EOC compared to the benign or healthy cohort. CONCLUSION: CircBNC2 is downregulated in EOC (both in tissue and plasma samples) and might present promising novel biomarker for EOC. Further studies are needed to verify our results. IMPACT: CircBNC2 is downregulated in EOC and warrants investigation in a screening study in females at risk for EOC.