Reduced Expression of TET1, TET2, TET3 and TDG mRNAs Are Associated with Poor Prognosis of Patients with Early Breast Cancer

PLoS One. 2015 Jul 24;10(7):e0133896. doi: 10.1371/journal.pone.0133896. eCollection 2015.

Abstract

Purpose: The purpose of this study was to determine the prognostic role of ten eleven translocation (TET) family proteins and DNA glycosylase (TDG) in patients with early breast cancer (EBC).

Methods: Expression of mRNAs encoding TET1-3 and TDG in 162 breast cancer tissues was quantified using real-time polymerase chain reaction analysis. The general characteristics of patients and clinicopathologic factors were collected. Estimation of patient survival was calculated using the Kaplan-Meier method, and independent prognostic indicators were analyzed using Cox regression analysis.

Results: The level of TET1 mRNA was significantly related to overall survival (OS) (P = 0.022). Multivariate analysis shows that the TNM stage was an independent predictor of disease-free survival (DFS) (HR = 1.761, 95% CI: 1.124-2.761, P = 0.014) and OS (HR = 2.135, 95% CI: 1.070-4.263, P = 0.032). Further, in patients with EBC who were treated with anthracyclines, Kaplan-Meier analysis indicates that the levels of TET3 and TDG mRNAs were related to DFS (P = 0.026 and 0.030, respectively), and multivariate analysis reveals that high levels of TET3 (HR = 1.944, 95% CI: 1.029-3.672, P = 0.040) and TDG (HR = 2.178, 95% CI: 1.140-4.163, P = 0.018) mRNAs were independent indicators of favorable DFS.

Conclusions: Our study indicates that EBC patients with decreased expression of TET1 mRNA had worse OS and that the levels of TET3 and TDG mRNAs were independent prognostic factors for patients who received anthracycline chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dioxygenases / genetics
  • Dioxygenases / metabolism*
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Humans
  • Middle Aged
  • Mixed Function Oxygenases
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Rate

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Mixed Function Oxygenases
  • TET1 protein, human
  • TET3 protein, human
  • Dioxygenases
  • TET2 protein, human
  • DNA Glycosylases

Grants and funding

This research is supported by grants from the National Natural Science Foundation of China (30971143, 30972936, and 81302303), the Shanghai United Developing Technology Project of Municipal Hospitals (SHDC12010116), the Key Clinical Program of the Ministry of Health (2010–2012), and the Shanghai Key laboratory of Breast Cancer (12DZ2260100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.