title: Metabolic profile of triple-negative breast cancer in African-American women reveals potential biomarkers of aggressive disease.
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.
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Kanaan
authors.affiliation: Metabolon Inc., Durham, NC, U.S.A.
authors.forename: Brante P
authors.initials: BP
authors.lastname: Sampey
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Desta
authors.initials: D
authors.lastname: Beyene
authors.affiliation: Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Ashwini K
authors.initials: AK
authors.lastname: Esnakula
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Tammey J
authors.initials: TJ
authors.lastname: Naab
authors.affiliation: Hampton University, Hampton, VA, U.S.A.
authors.forename: Luisel J
authors.initials: LJ
authors.lastname: Ricks-Santi
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dasi
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Agnes
authors.initials: A
authors.lastname: Day
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Kwesi W
authors.initials: KW
authors.lastname: Blackman
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Wayne
authors.initials: W
authors.lastname: Frederick
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Copeland
authors.affiliation: Johns Hopkins Cancer Center, Baltimore, MD, U.S.A.
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
authors.affiliation: Howard University, Washington, DC, U.S.A.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dewitty
mesh_terms: D001741:Black or African American; D000596:Amino Acids / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008745:Methylation; D008875:Middle Aged; D009243:NAD / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010084:Oxidation-Reduction; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor; D004151:Dipeptides; D009243:NAD; D005978:Glutathione
keywords: African-American women; Metabolomic; triple-negative breast cancer