Breast Cancer Research and Treatment

, Volume 117, Issue 1, pp 131–140

High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-β1

Authors

  • Biyun Qian
    • Department of Epidemiology and Public Health, Yale Cancer CenterYale University School of Medicine
    • Tianjin Medical University Cancer Institute and Hospital
  • Dionyssios Katsaros
    • Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer UnitUniversity of Turin
  • Lingeng Lu
    • Department of Epidemiology and Public Health, Yale Cancer CenterYale University School of Medicine
  • Mario Preti
    • Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer UnitUniversity of Turin
  • Antonio Durando
    • Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer UnitUniversity of Turin
  • Riccardo Arisio
    • Department of PathologyS’Anna Hospital
  • Lina Mu
    • Department of Epidemiology and Public Health, Yale Cancer CenterYale University School of Medicine
    • Department of Social and Preventive Medicine, School of Public Health and Health ProfessionsUniversity at Buffalo, The State University of New York
    • Department of Epidemiology and Public Health, Yale Cancer CenterYale University School of Medicine
Epidemiology

DOI: 10.1007/s10549-008-0219-7

Cite this article as:
Qian, B., Katsaros, D., Lu, L. et al. Breast Cancer Res Treat (2009) 117: 131. doi:10.1007/s10549-008-0219-7

Abstract

MicroRNA-21 (miR-21) is considered an onco-microRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-β) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-β, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan® microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-β1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08–4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-β may up-regulate its expression.

Keywords

Breast cancer miR-21 TGF-β Survival Stage

Copyright information

© Springer Science+Business Media, LLC. 2008