Circulating ciRS-7 as a potential non-invasive biomarker for epithelial ovarian cancer: An investigative study

Abstract

Background

Ovarian cancer (OC) is the most common malignant neoplasm of the female reproductive system in developed countries. Early detection, diagnosis and prognosis are particularly important to OC. The potential of circulating circular RNAs (circRNAs) as non-invasive biomarkers of various tumors has been especially described in recent years. The aim of this study was to explore the diagnostic and prognostic value of circulating cirRS-7 in patients with epithelial ovarian cancer (EOC).

Methods

Pre- and postoperative plasma samples from 111 EOC patients (47 cases with FIGO stage IA-IIB and 64 cases with FIGO stage IIB-IV) and healthy female volunteers was collected. Circulating ciRS-7 and hsa-miR-7-5p was analyzed using reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic and prognostic value of circulating cirRS-7 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan–Meier analysis.

Results

The preoperative expression levels of circulating ciRS-7 were increased in plasma of EOC FIGO stage I-IV patients than in the healthy controls (p < 0.001). However, the expression levels of ciRS-7 in the postoperative period were significantly lower in EOC FIGO stage IIA-IIA patients than healthy controls and EOC FIGO stage IIB-IV patients (p < 0.05, p < 0.001). The AUC of ciRS-7 for diagnosing EOC FIGO stage I-IV patients in pre-and postoperative periods was 0.90, 0.92, 0.84, 0.88, 0.58 and 0.86, respectively. Higher circulating ciRS-7 expression is associated with lymph node invasion, FIGO stage, distant metastasis, and worse overall survival (OS) of patients. Moreover, multivariate Cox analysis showed that higher circulating ciRS-7 was an independent predictor of OS in EOC FIGO stage IIB-IV patients. In addition, in plasma of EOC patients, ciRS-7 negatively correlated with has-miR-7-5p in pre-and postoperative periods (p < 0.001).

Conclusions

Circulating ciRS-7 levels in plasma can be considered a potential candidate biomarker for diagnosing EOC patients. Dysregulation of ciRS-7 may participate in the molecular mechanism of EOC through hsa-miR-7-5p sponging.