Cancer Genomics - Proteomics | |
Metabolic Profile of Triple-negative Breast Cancer in African-American Women Reveals Potential Biomarkers of Aggressive Disease | |
KWESI W. BLACKMAN3  BRANTE P. SAMPEY1  TAMMEY J. NAAB3  EDWARD GABRIELSON2  ASHWINI K. ESNAKULA4  DESTA BEYENE3  AGNES DAY3  SYLVIA DASI3  YASMINE M. KANAAN3  ROBERT L. COPELAND SR.3  ROBERT L. DEWITTY JR.3  LUISEL J. RICKS-SANTI5  WAYNE FREDERICK3  | |
[1] Metabolon Inc., Durham, NC, U.S.AMetabolon Inc., Durham, NC, U.S.AMetabolon Inc., Durham, NC, U.S.A;Johns Hopkins Cancer Center, Baltimore, MD, U.S.AJohns Hopkins Cancer Center, Baltimore, MD, U.S.AJohns Hopkins Cancer Center, Baltimore, MD, U.S.A;Howard University, Washington, DC, U.S.AHoward University, Washington, DC, U.S.AHoward University, Washington, DC, U.S.A;Cleveland Clinic, Cleveland, OH, U.S.ACleveland Clinic, Cleveland, OH, U.S.ACleveland Clinic, Cleveland, OH, U.S.A;Hampton University, Hampton, VA, U.S.AHampton University, Hampton, VA, U.S.AHampton University, Hampton, VA, U.S.A | |
关键词: Metabolomic; triple-negative breast cancer; African-American women; | |
DOI : | |
来源: Delinasios GJ CO | |
【 摘 要 】
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.
【 授权许可】
Unknown
【 预 览 】
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RO201912010183810ZK.pdf | 503KB | download |