Expression Analysis of miR-29b in Malignant and Benign Breast Tumors: A Promising Prognostic Biomarker for Invasive Ductal Carcinoma With a Possible Histotype-Related Expression Status

Clin Breast Cancer. 2018 Aug;18(4):305-312.e3. doi: 10.1016/j.clbc.2017.11.007. Epub 2017 Nov 21.

Abstract

Background: Aberrations in microRNA levels seem to provide valuable information regarding breast cancer prognosis and therapy. In this study, we sought to analyze miR-29b expression in breast tumors and thus explore its clinical value.

Materials and methods: One hundred twenty-one malignant and 56 benign breast tissue specimens were collected and subjected to extraction of total RNA, which was polyadenylated and reverse transcribed to cDNA. Subsequently, a highly sensitive quantitative real-time polymerase chain reaction protocol was developed and miR-29b levels, estimated via the comparative CT method, were finally subjected to comprehensive statistical analysis.

Results: MiR-29b levels did not differ between the analyzed benign and malignant breast tissue specimens, but were found to be significantly (P = .010) decreased in invasive ductal adenocarcinomas compared with their lobular counterparts, albeit receiver operating characteristics curve analysis did not verify the latter correlation. Additionally, miR-29b expression was elevated in samples with positive estrogen receptor status (P = .021) in the overall population, whereas it was negatively correlated (P = .035) with primary tumor staging in the ductal subset and increased in poorly-differentiated tumors of lobular origin (P = .041). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with ductal carcinoma and elevated miR-29b levels had a significantly longer disease-free survival (P = .010) and a lower risk to relapse (hazard ratio = 0.35, 95% confidence interval, 0.15-0.81; P = .014).

Conclusion: Our results provide evidence that miR-29b levels constitute a promising biomarker of favorable prognosis for patients with invasive ductal breast carcinoma and imply that its expression status might be affected by the histological origin of breast malignancy.

Keywords: Lobular; Mammary gland neoplasia; MicroRNAs; Molecular tumor markers; Quantitative real-time polymerase chain reaction.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Ductal, Breast / therapy
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / therapy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • MIRN29a microRNA, human
  • MicroRNAs