Am J Cancer Res 2012;2(1):104-115

Original Article
Expression of FOXO1 is associated with GATA3 and Annexin-1 and predicts
disease-free survival in breast cancer   

Yanyuan Wu, Yayha Elshimali, Marianna Sarkissyan, Hezla Mohamed, Sheila Clayton, Jaydutt V. Vadgama

Division of Cancer Research and Training, Departments of Internal Medicine; Pathology, and Surgery; Charles R. Drew
University of Medicine and Science, Jonsson Comprehensive Cancer Center and David Geffen UCLA School of Medicine, Los
Angeles, CA, USA

Received October 19, 2011; accepted November 7, 2011; Epub November 21, 2011; Published January 1, 2012

Abstract: Purpose: To determine the prognostic value of FOXO1, GATA3 and Annexin-1 expression in breast cancer. Methods:
Tissue microarray and individual paraffin tissue slides from 131 patients were used for the study. The association of FOXO1,
GATA3 and Annexin-1 expression with clinicopathological features of breast cancer and disease outcome was examined in
retrospective samples. Kaplan-Meier survival curves and Cox regression with multivariate analysis were used for assessing the
relative risk (RR) and disease-free survival (DFS). The expression of FOXO1, GATA3 and Annexin-1 were determined by
immunohistochemistry and the association among the three proteins was analyzed by Logistic regression analysis. Results:
The nuclear expression of FOXO1 was observed in most of the normal breast tissues and 51.3% of the malignant breast
tissues. GATA3 and Annexin-1 were expressed at 73% and 24.6% respectively in breast cancer tissues. The expression of
FOXO1, GATA3 and Annexin-1 were all inversely correlated with lymph node-positive tumors. Both FOXO1 and Annexin-1
expression were also inversely associated with HER2-overexpressing tumors. FOXO1 expression was significantly associated
with both GATA3 and Annexin-1 expression. In addition, Multivariate analyses confirm that only FOXO1 levels independently
predict DFS. Conclusion: FOXO1 expression in breast cancer is regulated by the PI3K/Akt pathway. The expression of FOXO1 is
also associated with GATA3 and/or Annexin-1. Restoring or targeting FOXO1 to the cell nucleus in breast cancer tissues may
improve response to therapy and disease outcome.  Further clinical studies are warranted to test this hypothesis.
(AJCR0000092).

Keywords: FOXO1, GATA3, annexin-1, survival, breast cancer

Full Text  PDF

Address all correspondence to:
Dr. Yanyuan Wu
Division of Cancer Research and Training
Charles R. Drew University of Medicine and Science
1731 East 120th Street
Los Angeles, CA 90059, USA.
Tel: 323-563-4853; Fax: 323-563-4859.
E-mail: yanyuanwu@cdrewu.edu
AJCR Copyright © 2010-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA
American Journal of Cancer Research
ISSN: 2156-6976