Metabolic profile of triple-negative breast cancer in African-American women reveals potential biomarkers of aggressive disease

Yasmine M. Kanaan, Brante P. Sampey, Desta Beyene, Ashwini K. Esnakula, Tammey J. Naab, Luisel J. Ricks-Santi, Sylvia Dasi, Agnes Day, Kwesi W. Blackman, Wayne A. I. Frederick, Robert L. Copeland, Edward Gabrielson, Robert L. Dewitty

Research output: Contribution to journalArticle

Abstract

Expression of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) can subdivide breast carcinomas into clinically meaningful classes. Cancers lacking expression of all three of these receptors (triple-negative breast cancer; TNBC) is of particular interest for molecular research because these tumors currently have no effective targets for therapy. Furthermore, TNBCs are relatively more prevalent among African-American women and can account for some of the health disparities associated with breast cancer. We approached a molecular understanding of how TNBC differs from ER+ breast cancer through a comprehensive gas chromatography (GC)-mass spectrometry (MS) and liquid chromatography (LC)/MS/MS-based and unbiased metabolomic analysis of a series of breast carcinomas from African-American patients. Remarkably, global metabolomic profiling of tumor tissues identified a total of 418 distinct metabolites, out of which 133 (31.8%) were shown to differ between the ER+ and TNBC tumors with statistical probability of p<0.05. Specific biochemical pathways affected included those reflecting general increases in energy metabolism and transmethylation in the TNBC tumors when compared to ER+ tumors. Additionally, biochemicals associated with increased proliferation, redox balance and the recently proposed oncometabolites, sarcosine and 2-hydroxyglutarate, were also detected at higher levels in the TNBC versus ER+ tumors. These studies demonstrate that TNBC tumors have metabolic signatures that distinguish them from ER+ tumors and suggest that distinctive metabolic characteristics of these tumors might offer new targets for treatment.

Original languageEnglish (US)
Pages (from-to)279-294
Number of pages16
JournalCancer Genomics and Proteomics
Volume11
Issue number6
StatePublished - Nov 1 2014

Keywords

  • African-American women
  • Metabolomic
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kanaan, Y. M., Sampey, B. P., Beyene, D., Esnakula, A. K., Naab, T. J., Ricks-Santi, L. J., Dasi, S., Day, A., Blackman, K. W., Frederick, W. A. I., Copeland, R. L., Gabrielson, E., & Dewitty, R. L. (2014). Metabolic profile of triple-negative breast cancer in African-American women reveals potential biomarkers of aggressive disease. Cancer Genomics and Proteomics, 11(6), 279-294.