The mRNA expression of inhibitors of DNA binding-1 and -2 is associated with advanced tumour stage and adverse clinical outcome in human breast cancer

Anticancer Res. 2013 May;33(5):2179-83.

Abstract

Inhibitors of DNA binding (ID) are known to have a role in embryogenesis and oncogenesis. In this study, we analyzed the role of ID1 and ID2 in breast cancer, by assessing associations of mRNA expression with clinicopathological parameters.

Materials and methods: Breast cancer tissues (n=152) and adjacent normal tissues (n=31) underwent reverse transcription and quantitative- polymerase chain reaction (qPCR). Transcript levels were correlated with clinicopathological data.

Results: Patients who were disease-free had significantly lower ID1 mRNA expression than all other patients (p=0.0033). Higher expression was associated with worse disease-free (p=0.001) and overall survival (p=0.02). ID2 expression was directly associated with the Nottingham Prognostic Index (NPI) (NPI 2 vs. 3; p=0.0062) and worsening clinical outcome (disease-free vs. mortality: p=0.0004), and with worse disease-free (p=0.01) and overall survival (p=0.005).

Conclusion: Our findings are suggestive of a role for ID1 and ID2 in human breast cancer as possible prognostic markers and therapeutic targets meriting further validating investigations, by immunohistochemistry and mechanistic studies.

Keywords: ID1; ID2; Inhibitor of differentiation; breast cancer; cell cycle; helix-loop-helix; inhibitor of DNA binding; qPCR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / secondary
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast / metabolism*
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / secondary
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Medullary / mortality
  • Carcinoma, Medullary / secondary
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Inhibitor of Differentiation Protein 1 / genetics*
  • Inhibitor of Differentiation Protein 1 / metabolism
  • Inhibitor of Differentiation Protein 2 / genetics*
  • Inhibitor of Differentiation Protein 2 / metabolism
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / metabolism
  • Neoplasm Grading
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • ID1 protein, human
  • ID2 protein, human
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • ID3 protein, human