Metabolic Profile of Triple-negative Breast Cancer in African-American Women Reveals Potential Biomarkers of Aggressive Disease

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 p0.05. 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.