title: ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression.
abstract: BACKGROUND
  Inhibitors of DNA-binding (ID) proteins are known as important modulators in the regulation of cell proliferation and differentiation. This study sought to investigate the prognostic value of ID proteins in breast cancer.
  
  
  METHODS
  The prognostic role of ID proteins in human breast cancer was investigated in 250 breast cancers, via tissue microarrays. The messenger (m)RNA and protein levels of E-cadherin were examined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting, in cells overexpressing IDs. Dual-luciferase report assay was used to investigate the potential mechanism, and a migration assay was performed to investigate the influence of IDs on cell migratory activity.
  
  
  RESULTS
  The survival analysis with Kaplan-Meier and Cox regression showed that ID2 expression level, which correlated with estrogen receptor status and E-cadherin abundance, served as an independent prognostic factor for disease-free survival (DFS) (P=0.013). The prognostic value of ID2 for DFS was most significant in triple-negative breast cancer patients (P=0.009). We also found that ID2 was negatively correlated with E-cadherin expression by correlation analysis (P=0.020, Pearson's R=-0.155). Subsequently, we explored the biological rationale and uncovered that the enforced expression of ID proteins could suppress E-cadherin expression significantly, thus increasing the migration ability of mammary epithelial cells. Then using a combination of ID2 and E-cadherin expression, the patients were classified into four subgroups with different DFS (P=0.023).
  
  
  CONCLUSIONS
  The overexpression of ID2 can be used as a prognostic marker in breast cancer patients, especially in triple-negative breast cancer patients. ID proteins were still, unexpectedly, revealed to inhibit E-cadherin abundance.
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China.
authors: Kai
authors: K
authors: Li
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China.
authors: Ling
authors: L
authors: Yao
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China.
authors: Li
authors: L
authors: Chen
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China.
authors: Zhi-Gang
authors: ZG
authors: Cao
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China.
authors: San-Jian
authors: SJ
authors: Yu
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China.
authors: Xia-Ying
authors: XY
authors: Kuang
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China.
authors: Xin
authors: X
authors: Hu
authors: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, People's Republic of China ; Department of Oncology, Shanghai Medical College, Shanghai, People's Republic of China ; Institutes of Biomedical Science, Fudan University, Shanghai, People's Republic of China.
authors: Zhi-Ming
authors: ZM
authors: Shao
keywords: biomarker; breast cancer; prognosis