Correlated expression of CD47 and SIRPA in bone marrow and in peripheral blood predicts recurrence in breast cancer patients

Clin Cancer Res. 2010 Sep 15;16(18):4625-35. doi: 10.1158/1078-0432.CCR-10-0349. Epub 2010 Aug 12.

Abstract

Purpose: CD47 plays a variety of roles in intercellular signaling. Herein, we focused on the clinicopathologic significance of CD47 expression in human breast cancer. Our data suggest that the correlation between CD47 and signal regulatory protein α (SIRPA) expression may play a key role in the progression of breast cancer.

Experimental design: Quantitative real-time PCR was used to evaluate CD47 mRNA and SIRPA mRNA expression in bone marrow and in peripheral blood from 738 cases of breast cancer.

Results: In patients with high levels of CD47 expression in the bone marrow, survival was significantly poorer compared with patients with low levels of CD47 expression [disease-free survival (DFS), P = 0.0035; overall survival (OS), P = 0.015]. Furthermore, high CD47 expression group in a multivariate analysis showed significance as an independent variable for poorer prognosis in DFS (P = 0.024). In the peripheral blood, however, high CD47 expression in patients was not an independent and significant prognostic factor for DFS and OS in a multivariate analysis. CD47 expression was strongly correlated with SIRPA expression in both the bone marrow (P < 0.0001) and peripheral blood (P < 0.0001) of breast cancer patients.

Conclusions: This is one of the first studies to show that a host factor in bone marrow confers prognostic importance. CD47 is an important biomarker in breast cancer, and functions as a prognostic factor for DFS. Moreover, we suggest that the poor prognosis of breast cancer patients with high expression of CD47 is due to an active CD47/SIRPA signaling pathway in circulating cells.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation / blood
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • Blood Cells / metabolism*
  • Blood Cells / pathology
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • CD47 Antigen / blood
  • CD47 Antigen / genetics*
  • CD47 Antigen / metabolism
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / diagnosis*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / mortality
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Molecular Diagnostic Techniques
  • Prognosis
  • Receptors, Immunologic / blood
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism
  • Recurrence
  • Survival Analysis
  • Young Adult

Substances

  • Antigens, Differentiation
  • CD47 Antigen
  • CD47 protein, human
  • Receptors, Immunologic
  • SIRPA protein, human