Role of miR-139 as a surrogate marker for tumor aggression in breast cancer

Hum Pathol. 2017 Mar:61:68-77. doi: 10.1016/j.humpath.2016.11.001. Epub 2016 Nov 15.


MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.

Keywords: Breast cancer; Invasive ductal carcinoma; Micro RNA; MicroRNA-139; Oncogenesis; Tumor progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / classification
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Phenotype
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Survival Analysis
  • Tumor Burden


  • Biomarkers, Tumor
  • MIRN139 microRNA, human
  • MicroRNAs