Plasma microRNA panel for minimally invasive detection of breast cancer

PLoS One. 2013 Oct 23;8(10):e76729. doi: 10.1371/journal.pone.0076729. eCollection 2013.

Abstract

Over the last few years, circulating microRNAs (miRNAs) have emerged as promising novel and minimally invasive markers for various diseases, including cancer. We already showed that certain miRNAs are deregulated in the plasma of breast cancer patients when compared to healthy women. Herein we have further explored their potential to serve as breast cancer early detection markers in blood plasma. Circulating miR-127-3p, miR-376a and miR-652, selected as candidates from a miRNA array-based screening, were found to be associated with breast cancer for the first time (n = 417). Further we validated our previously reported circulating miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) in an independent cohort (n = 210) as elevated in the plasma of breast cancer patients compared to healthy women. We described, for the first time in breast cancer, an over-representation of deregulated miRNAs (miR-127-3p, miR-376a, miR-376c and miR-409-3p) originating from the chromosome 14q32 region. The inclusion of patients with benign breast tumors enabled the observation that miR-148b, miR-652 and miR-801 levels are even elevated in the plasma of women with benign tumors when compared to healthy controls. Furthermore, an analysis of samples stratified by cancer stage demonstrated that miR-127-3p, miR-148b, miR-409-3p, miR-652 and miR-801 can detect also stage I or stage II breast cancer thus making them attractive candidates for early detection. Finally, ROC curve analysis showed that a panel of these seven circulating miRNAs has substantial diagnostic potential with an AUC of 0.81 for the detection of benign and malignant breast tumors, which further increased to 0.86 in younger women (up to 50 years of age).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / diagnosis*
  • Chromosomes, Human, Pair 14 / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • MicroRNAs* / blood
  • MicroRNAs* / genetics
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • MIRN127 microRNA, human
  • MIRN148 microRNA, human
  • MIRN376 microRNA, human
  • MIRN652 microRNA, human
  • MicroRNAs

Grant support

This study was supported by the Dietmar-Hopp Foundation, Helmholtz Society and German Cancer Research Center (DKFZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.