Metabolic pathways of potential miRNA biomarkers derived from liquid biopsy in epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the type of OC with the highest mortality rate. Due to the asymptomatic nature of the disease and few available diagnostic tests, it is mostly diagnosed at the advanced stage. Therefore, the present study aimed to discover predictive and/or early diagnostic novel circulating microRNAs (miRNAs or miRs) for EOC. Firstly, microarray analysis of miRNA expression levels was performed on 32 samples of female individuals: Eight plasma samples from patients with pathologically confirmed EOC (mean age, 45 (30-54) years), eight plasma samples from matched healthy individuals (HIs) (mean age, 44 (30-65) years), eight EOC tissue samples (mean age, 45 (30-54) years) and eight benign ovarian (mean age, 35 (17-70) years) neoplastic tissue samples A total of 31 significantly dysregulated miRNAs in serum and three miRNAs in tissue were identified by microarray. The results were validated using reverse transcription-quantitative PCR on samples from 10 patients with pathologically confirmed EOC (mean age, 47(30-54) years), 10 matched His (mean age, 40(26-65) years], 10 EOC tissue samples (mean age, 47(30-54) years) and 10 benign ovarian neoplastic tissue samples (mean age, 40(17-70) years). The 'Kyoto Encyclopedia of Genes and Genomes' (KEGG) database was used for target gene and pathway analysis. A total of three miRNAs from EOC serum (hsa-miR-1909-5p, hsa-miR-885-5p and hsa-let-7d-3p) and one microRNA from tissue samples (hsa-miR-200c-3p) were validated as significant to distinguish patients with EOC from HIs. KEGG pathway enrichment analysis showed seven significant pathways, which included 'prion diseases', 'proteoglycans in cancer', 'oxytocin signaling pathway', 'hippo signaling pathway', 'adrenergic signaling in cardiomyocytes', 'oocyte meiosis' and 'thyroid hormone signaling pathway', in which the validated miRNAs served a role. This supports the hypothesis that four validated miRNAs, have the potential to be a biomarker of EOC diagnosis and target for treatment.