Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as an indicator for poor clinical outcome and tamoxifen resistance

Oncotarget. 2017 May 30;8(22):36305-36318. doi: 10.18632/oncotarget.16750.

Abstract

The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog, Bmi1, and Klf4, are known to be associated with stemness, epithelial-mesenchymal transition and aggressive tumor behavior. This study was designed to evaluate the clinicopathological significance of their expression in breast cancer. Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319 cases of invasive breast cancer. The relationship between the expression of these markers and clinicopathologic features of the tumors, including breast cancer stem cell phenotype and epithelial-mesenchymal transition marker expression, and their prognostic value in breast cancer, were analyzed. Expression of Oct4 and Sox2 was commonly associated with high histologic grade and high Ki-67 index in the whole group and in the hormone receptor-positive subgroup. On the other hand, expression of Nanog, Bmi1, and Klf4 was inversely correlated with aggressive features of the breast cancer. Oct4 expression was associated with ALDH1 expression but not with epithelial-mesenchymal transition marker expression. In survival analysis, Oct4 expression was independently associated with poor prognosis in the whole group and in the hormone receptor-positive subgroup, but not in hormone receptor-negative subgroup. Particularly, Oct4 expression was associated with poor clinical outcome in patients with hormone receptor-positive breast cancer treated with tamoxifen. Our results indicate that Oct4 expression is associated with aggressive features, ALDH1 expression, tamoxifen resistance and poor clinical outcomes in hormone receptor-positive breast cancer, and thus may be useful as a predictive and prognostic marker in this subgroup of breast cancer.

Keywords: Oct4; breast cancer; cancer stem cell; prognosis; tamoxifen resistance.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Combined Modality Therapy / methods
  • Drug Resistance, Neoplasm / genetics
  • Embryonic Stem Cells / metabolism*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Octamer Transcription Factor-3 / genetics*
  • Phenotype
  • Prognosis
  • Survival Analysis
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use
  • Transcription Factors / genetics*

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Transcription Factors
  • Tamoxifen