Expression of serum miR-200a, miR-200b, and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features

Clin Transl Oncol. 2015 Oct;17(10):779-87. doi: 10.1007/s12094-015-1303-1. Epub 2015 Jun 11.

Abstract

Background: MicroRNAs (miRs) have been implicated in the etiology of various human cancers. The aim of this study was to investigate the association of the expression of three members--miR 200a, miR 200b, and miR 200c belonging to the miR-200 family with clinicopathological characteristics and their impact on the progression of epithelial ovarian cancer (EOC).

Materials and methods: Total RNA from serum was isolated by Trizol method, polyadenylated, and reverse transcribed into cDNA. Expression levels of miR-200a, miR-200b, and miR-200c were detected by using miRNA qRT-PCR. We measured miR expression in 70 serum samples of EOC patients with matched controls using U6 snRNA as a reference. Levels of miR expression was compared with distinct clinicopathological features.

Results: Expression of miR-200a was found to be greater than six-fold (p = 0.01), miR-200b and miR-200c greater than three-fold (p = 0.01) in comparison with matched normal controls. Association of miRNA expression with clinicopathological factors and progression was statistically evaluated. The expression levels of miR-200a and miR-200c were found to be significantly associated with disease progression (p = 0.04 and p < 0.001, respectively). miR-200a overexpression was found be associated with tumor histology and stage. Patients with lymph node metastasis showed significant elevation of miR-200c (p = 0.006). The AUC in ROC curve also indicated that serum levels of miR-200a and miR-200c might be worthwhile as a diagnostic tool in the near future.

Conclusion: Our findings suggest that miR-200a, miR-200b, and miR-200c overexpressions are associated with the aggressive tumor progression and be recognized as reliable markers to predict the prognosis and survival in EOC patients.

Keywords: Biomarker; Disease progression; Overexpression; qRT-PCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / blood
  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / blood
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Adenocarcinoma, Papillary / blood
  • Adenocarcinoma, Papillary / genetics
  • Adenocarcinoma, Papillary / pathology
  • Adult
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Endometrioid / blood
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Cystic, Mucinous, and Serous / blood
  • Neoplasms, Cystic, Mucinous, and Serous / genetics
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Neoplasms, Glandular and Epithelial / blood
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Tumor Burden
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MIRN200 microRNA, human
  • MicroRNAs