Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer

PLoS One. 2013 Nov 1;8(11):e77853. doi: 10.1371/journal.pone.0077853. eCollection 2013.

Abstract

Background: Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.

Methodology/principal findings: We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients.

Conclusions/significance: Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • MIRN205 microRNA, human
  • MicroRNAs
  • mirnlet7 microRNA, human

Grants and funding

This work was supported partially by the National Natural Science Foundation of China (Grants 81072363), the program for Changjiang Scholars and Innovative Research Team at the University in China (Grant IRT1076), the National Key Scientific and Technological Project (Grant 2011ZX09307-001-04), and the Tianjin Science and Technology Committee Foundation (Grant 09ZCZDSF04700). The tissue bank is jointly supported by the Tianjin Center and the US National Foundation for Cancer Research. D.Y. is an Odyssey Fellow at MD Anderson Cancer Center, and supported by The Diane Denson Tobola Fellowship in Ovarian Cancer Research fellowship and The Harold C. and Mary L. Daily Endowment Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.