Detection of 14-3-3 sigma (σ) promoter methylation as a noninvasive biomarker using blood samples for breast cancer diagnosis

Oncotarget. 2017 Feb 7;8(6):9230-9242. doi: 10.18632/oncotarget.13992.

Abstract

As a tumor suppressor gene, 14-3-3 σ has been reported to be frequently methylated in breast cancer. However, the clinical effect of 14-3-3 σ promoter methylation remains to be verified. This study was performed to assess the clinicopathological significance and diagnostic value of 14-3-3 σ promoter methylation in breast cancer. 14-3-3 σ promoter methylation was found to be notably higher in breast cancer than in benign lesions and normal breast tissue samples. We did not observe that 14-3-3 σ promoter methylation was linked to the age status, tumor grade, clinic stage, lymph node status, histological subtype, ER status, PR status, HER2 status, or overall survival of patients with breast cancer. The combined sensitivity, specificity, AUC (area under the curve), positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and post-test probability values (if the pretest probability was 30%) of 14-3-3 σ promoter methylation in blood samples of breast cancer patients vs. healthy subjects were 0.69, 0.99, 0.86, 95, 0.31, 302, and 98%, respectively. Our findings suggest that 14-3-3 σ promoter methylation may be associated with the carcinogenesis of breast cancer and that the use of 14-3-3 σ promoter methylation might represent a useful blood-based biomarker for the clinical diagnosis of breast cancer.

Keywords: 14-3-3 σ; biomarker; blood; breast cancer; diagnosis; promoter methylation.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • 14-3-3 Proteins / blood
  • 14-3-3 Proteins / genetics*
  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / therapy
  • Case-Control Studies
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics*
  • DNA Methylation*
  • Disease Progression
  • Disease-Free Survival
  • Exoribonucleases / blood
  • Exoribonucleases / genetics*
  • Female
  • Humans
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Odds Ratio
  • Predictive Value of Tests
  • Promoter Regions, Genetic*
  • ROC Curve
  • Reproducibility of Results
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Exoribonucleases
  • SFN protein, human