Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer
Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is expressed at a low level in normal breast epithelium but is detectably expressed in approximately 50–60% of primary human breast tumors. We have derived an eEF1A2-specific antibody and measured eEF1A2 protein expression in a sample of 438 primary breast tumors annotated with 20-year survival data. We find that high levels of eEF1A2 protein are detected in 60% of primary breast tumors independent of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor of outcome. Women whose tumor has high eEF1A2 protein expression have an increased probability of 20-year survival compared to those women whose tumor does not express substantial eEF1A2. In addition, eEF1A2 protein expression predicts increased survival probability in those breast cancer patients whose tumor is HER-2 negative or who have lymph node involvement.
KeywordsOncogene Protein translation eEF1A2 Prognostic factor Tissue microarray Gene expression
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This work was supported by funding from the Canadian Breast Cancer Research Alliance (CBCRA), an Idea Grant from the US Army and the National Cancer Institute of Canada (JML). MAA is a Canada Research Chair in Bioinformatics. We thank Jessica Rousseau for technical assistance, and Carolina Perez-Iratxeta for assistance in the analysis of the DNA microarray data. We thank Stephen Lee, Dixie Pinkie, Illona Skerjanc, Barbara Vanderhyden, and Zemin Yao for helpful discussions and critical reading of this article. We thank Maggie C.U. Cheang, Andy K.W. Chan and Samuel Leung for creation and maintenance of publicly available GPEC image database. We thank Vladimira J. Pavlova for preparation of TMA immunostained sections. We gratefully acknowledge Dr. Joseph Nevins for making breast cancer gene expression data publicly available.
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