Role of a novel circulatory RNA-based biomarker panel expression in ovarian cancer

IUBMB Life. 2019 Dec;71(12):2031-2047. doi: 10.1002/iub.2153. Epub 2019 Sep 13.

Abstract

Ovarian cancer (OC) is considered the sixth commonest cancer affecting women globally. We choose novel integrated specific ovarian cancer RNA biomarker panel; pellino E3 ubiquitin protein ligase family member 3 (PELI3) gene expressions along with its selected epigenetic regulators (microRNA (miR-361-3p) and long noncoding RNA (lncRNA RP5-837J1.2) by bioinformatic methods. Then, differential expressions of the selected panel in the sera of 50 OC patients, 42 cases with benign ovarian lesions, and among 45 controls were determined using real-time polymerase chain reaction quantitative (qRT-PCR). Furthermore, their expression was measured also in malignant ovarian tissues and adjacent nontumor tissues in 23 of 50 OC patients by quantitative qRT-PCR. The current study reported, for the first time, upregulation of serum lncRNA RP5-837J1.2 with concomitant downregulation of miR-361-3p and PELI3 mRNA in malignant group compared with benign and controls groups. There were associations of serum lncRNA RP5-837J1.2 with the affected ovary and worse International Federation of Gynecology and Obstetrics staging; associations of miR-361-3p with tumor size, grade, stage, and presence of metastasis; as well as associations among PELI3 mRNA expression and tumor size, grade, stage, and presence of metastasis among the OC group. In tumor tissues, miR-361-3p and PELI3 mRNA levels were at a higher level than that of nontumor tissues; however, tumor tissue showed lower level of lncRNA RP5-837J1.2 compared to normal tissue. There were positive correlations between serum and tissue level of RNA RP5-837J1.2, miR-361-3p, and PELI3 mRNA, but they did not reach statistical significance. Receiver operating characteristics curve analyses showed that lncRNA RP5-837J1.2, miR-361-3p, and PELI3 mRNA expression levels can discriminate among OC patient, cases with benign mass, and controls with an accuracy of 96, 76, and 83%, respectively; which increased if they are combined. This novel diagnostic RNA-based panel biomarker could be helpful for OC diagnosis.

Keywords: bioinformatics; long noncoding RNA; micro-RNA; ovarian cancer; real-time PCR; toll like receptors.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Ubiquitin-Protein Ligases / blood
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Biomarkers, Tumor
  • MIRN361 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • PELI3 protein, human
  • Ubiquitin-Protein Ligases