Circulating tumour cell-derived plastin3 is a novel marker for predicting long-term prognosis in patients with breast cancer

Br J Cancer. 2015 Apr 28;112(9):1519-26. doi: 10.1038/bjc.2015.132. Epub 2015 Apr 16.

Abstract

Background: Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer.

Methods: We examined PLS3 expression in breast cancer cell lines with epithelial and mesenchymal traits and in circulating tumour cells (CTCs) obtained from the peripheral blood of breast cancer patients. We investigated PLS3 expression in the peripheral blood of 594 patients with breast cancer to evaluate the clinical significance of PLS3 expression.

Results: Robust PLS3 expression was observed in different breast cancer cell lines (Hs578t, MCF-7, MDA-MB-468, and MDA-MB-231) as well as in a bone marrow derived cancer cell line (BC-M1). In both the training (n=298) and validation (n=296) sets, PLS3 expression was observed in CTCs of patients with breast cancer. PLS3-positive patients showed significantly poorer overall and disease-free survival than PLS3-negative patients (P=0.0001 and 0.003, respectively). Subset analysis revealed that this prognostic biomarker was relevant in patients with stage I-III cancer, particularly in patients with luminal-type and triple-negative-type tumours.

Conclusions: These data demonstrated that PLS3 was expressed in CTCs undergoing the epithelial-mesenchymal transition in patients with breast cancer. Furthermore, PLS3 may be an excellent biomarker for identifying groups at risk of recurrence or with a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Blotting, Western
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Epithelial-Mesenchymal Transition*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / blood*
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / blood*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • Microfilament Proteins
  • RNA, Messenger
  • plastin