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

  • Biyun Qian
  • Dionyssios Katsaros
  • Lingeng Lu
  • Mario Preti
  • Antonio Durando
  • Riccardo Arisio
  • Lina Mu
  • Herbert Yu
Epidemiology

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 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Biyun Qian
    • 1
    • 2
  • Dionyssios Katsaros
    • 3
  • Lingeng Lu
    • 1
  • Mario Preti
    • 3
  • Antonio Durando
    • 3
  • Riccardo Arisio
    • 4
  • Lina Mu
    • 1
    • 5
  • Herbert Yu
    • 1
  1. 1.Department of Epidemiology and Public Health, Yale Cancer CenterYale University School of MedicineNew HavenUSA
  2. 2.Tianjin Medical University Cancer Institute and HospitalTianjinChina
  3. 3.Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer UnitUniversity of TurinTurinItaly
  4. 4.Department of PathologyS’Anna HospitalTurinItaly
  5. 5.Department of Social and Preventive Medicine, School of Public Health and Health ProfessionsUniversity at Buffalo, The State University of New YorkBuffaloUSA

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