Circular RNA profiling reveals circEXOC6B and circN4BP2L2 as novel prognostic biomarkers in epithelial ovarian cancer

Int J Oncol. 2018 Dec;53(6):2637-2646. doi: 10.3892/ijo.2018.4566. Epub 2018 Sep 20.


Circular RNAs (circRNAs) are regarded as a novel class of widespread endogenous non-coding RNAs, which may play important roles in tumorigenesis by regulating gene expression. Nevertheless, the characterization of circRNAs in epithelial ovarian cancer (EOC) remains largely unknown. This study aimed to investigate circRNA expression profiles in EOC. A total of 54 EOC specimens and 54 normal ovarian tissues (controls) were collected. circRNA-sequencing based circRNA expression profiles were identified in 4 EOC specimens and compared with 4 normal ovarian tissues. circRNA-sequencing data were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the 54 EOC specimens and 54 normal ovarian tissues. The association between differentially expressed circRNAs and various clinicopathological features of EOC was determined using a non-parametric test. Univariate analysis was performed using the log-rank test. A total of 4,388 circRNAs (2,556 up- and 1,832 downregulated; fold change of ≥2 and P<0.05) were identified to be differentially expressed in the EOC specimens compared with the normal ovarian tissues. Of these, the levels of 6 circRNAs (circBNC2, circEXOC6B, circFAM13B, circN4BP2L2, circRHOBTB3 and circCELSR1) were confirmed by RT-qPCR. Our data further indicated that these 6 circRNAs were associated with various clinicopathological features of EOC. More importantly, we found that circEXOC6B and circN4BP2L2 may act as novel prognostic biomarkers in patients with EOC. On the whole, the results of this study indicate that differentially expressed circRNAs may participate in the pathogenesis of EOC and may thus have potential for use as novel diagnostic and prognostic biomarkers for EOC. Future experiments with larger sample sizes are required to verify the current findings and illuminate the regulatory mechanisms of action of circRNAs in the tumorigenesis of EOC.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / pathology
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA / genetics*
  • RNA, Circular
  • Sequence Analysis, RNA / methods


  • Biomarkers, Tumor
  • RNA, Circular
  • RNA