The Role of Breast Cancer Stem Cells and Some Related Molecular Biomarkers in Metastatic and Nonmetastatic Breast Cancer

Clin Breast Cancer. 2020 Aug;20(4):e373-e384. doi: 10.1016/j.clbc.2019.11.008. Epub 2020 Mar 12.

Abstract

Background: Breast cancer stem cells (BCSCs) play important role(s) in the development and progression of invasive duct carcinoma (IDC). We assessed the role of BCSC marker expression and the number of mammospheres in cultures of breast cancer (BC) tissues and correlated these data to relevant clinicopathologic features of the patients and overall survival (OS).

Methods: Fresh tumor tissue samples were collected from 44 Egyptian female patients with IDC of the breast and 25 healthy women undergoing reduction mammoplasty as a control. The mammosphere number and the RNA expression levels of some cancer stem cell-related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) were assessed by reverse-transcriptase polymerase chain reaction at different stages of BCSC differentiation compared with control samples.

Results: The number of CD44+CD24-/low cells associated significantly at the end of culture with the expression level of Wnt, β-catenin, and distant metastasis (P < .001, P = .015 and P = .003, respectively). There was significant association between the mammosphere number and CD44+CD24-/low cells as well as AKT expression (P = .040 and .021, respectively). PTEN messenger RNA expressed significantly in BC (P < .05). Wnt-RNA expression associated significantly with high tumor stage, positive lymph node status, Her2-neu overexpression, and metastasis (P = .009, .012, .026, and .001, respectively), whereas OS associated significantly with distant metastasis, Wnt, and PTEN expressions (P < .001, P = .001, P = .014, respectively).

Conclusion: BCSCs and their related genes (PTEN, PI3K, AKT, Wnt, and β-catenin) play important roles in the development and progression of BC and they can be used as potential prognostic and predictive biomarkers for patients with BC or as target therapy.

Keywords: AKT; BCSCs; Mammospheres; PI3K; PTEN; Wnt; β-catenin.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Breast / pathology*
  • Breast / surgery
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Ductal, Breast / therapy
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Stem Cells / pathology*
  • Primary Cell Culture
  • Retrospective Studies
  • Signal Transduction / genetics
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Biomarkers, Tumor