Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer

PLoS One. 2013;8(2):e56919. doi: 10.1371/journal.pone.0056919. Epub 2013 Feb 20.

Abstract

Triple negative breast cancer (TNBC) acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025), the proliferation marker Ki-67 (P = 0.001), and the recurrence rate of TNBC patients (P<0.001). In TNBC patients with Aur-A high expression, the risk of distant recurrence peaked at the first 3 years and declined rapidly thereafter, whereas patients with Aur-A low expression showed a relatively constant risk of recurrence during the entire follow-up period. Univariate and multivariate analysis showed that overexpression of Aur-A predicted poor overall survival (P = 0.002) and progression-free survival (P = 0.012) in TNBC. Furthermore, overexpression of Aur-A, associated with high Ki-67, predicted an inferior prognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aurora Kinases
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Piperazines / pharmacology
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Recurrence

Substances

  • Ki-67 Antigen
  • Piperazines
  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • tozasertib
  • Receptor, ErbB-2
  • Aurora Kinases
  • Protein Serine-Threonine Kinases

Grants and funding

The work was supported by a National Nature Science Foundation of China (Grant No. 81101521 to J. Wang, Grant No. 81160305 to A.W. Liu and Grant No. 81160306 to J.B. Wu), the National Science Fund for Distinguished Young Scholars (Grant No. 30888003 to Q. Liu), the State Key Program of National Natural Science of China (Grant No. 81130040 to Q. Liu), and 973 Project from the Ministry of Science and Technology of China (Grants No. 2012CB967000 to Q. Liu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.