MiR-27 as a prognostic marker for breast cancer progression and patient survival

PLoS One. 2012;7(12):e51702. doi: 10.1371/journal.pone.0051702. Epub 2012 Dec 11.

Abstract

Background: MicroRNA-27a (miR-27a) is thought to be an onco-microRNA that promotes tumor growth and metastasis by downregulating ZBTB10. The potential predictive value of miR-27a was studied in breast cancer patients.

Methods: The expression of miR-27a and ZBTB10 was examined in 102 breast cancer cases using in situ hybridization (ISH) and immunohistochemistry techniques and were evaluated semi-quantitatively by examining the staining index. The Correlation of miR-27a and ZBTB10 expression was analyed by Spearman Rank Correlation. The association of miR-27a and ZBTB10 expression with clinicopathological characteristics was analyzed using the χ(2) test, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic values of miR-27a and ZBTB10.

Results: miR-27a was markedly up-regulated in invasive breast cancers that expressed low levels of ZBTB10 (P<0.001). A reverse correlation between miR-27a and ZBTB10 was also observed in breast cancer tissue samples (r(s) = -0.478, P<0.001). Furthermore, the expression of miR-27a and ZBTB10 was significantly correlated with clinicopathological parameters, including tumor size, lymph node metastasis and distant metastasis (P<0.05), but not with receptor status. Patients with high miR-27a or low ZBTB10 expression tended to have significantly shorter disease-free survival times (57 months and 53 months, respectively, P <0.001) and overall survival times (58 months and 55 months, respectively, P <0.001). Univariate and multivariate analysis showed that both miR-27a and ZBTB10 were independent prognostic factors of disease-free survival in breast cancer patients (P <0.001), while only miR-27a was an independent predictor of overall survival (P <0.001).

Conclusions: High miR-27a expression is associated with poor overall survival in patients with breast cancer, which suggests that miR-27a could be a valuable marker of breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Disease-Free Survival*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Prognosis
  • Repressor Proteins* / genetics
  • Repressor Proteins* / metabolism

Substances

  • Biomarkers, Tumor
  • MIRN27 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • ZBTB10 protein, human

Grants and funding

This work was supported by Natural Science Foundation of China grants (30921140312, 30973396, 30830110, 30972785 and 81172524), a Clinical Key Project of the Public Health Administration of China, a grant for Development of Important New Drugs from the Ministry of Health of China (2011ZX09102-010-02) and a Young Teacher grant from the HuoYingdong Educational Foundation (121042). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.