Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and characterized by covalently closed loop without 5' and 3' end. Recently, the diagnostic value of circRNAs has received more and more attention. However, the in-depth study about circRNAs diagnosis in breast cancer is still rarely reported. In present study, we try to investigate the circRNAs expression profiles in breast cancer peripheral blood and discover valuable diagnostic biomarkers.

The expression profiles of circRNAs in plasma specimens were screened from five breast cancer and paired healthy volunteer s. The expression levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve.

CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with 2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among these circRNAs, 3 candidate circRNAs were validated to be significantly dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover, in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3 (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients (0.283±0.043) was significantly lower than that of preoperative patients (0.109±0.037, P<0.01).

Our study reveals the aberrant circRNAs expression profiles in breast cancer peripheral blood, and identifies the potential diagnostic value of plasma hsa_circ_0001785, providing a stable biomarkers for the diagnosis and progress of breast cancer.