Metabolic profiles of triple-negative and luminal A breast cancer subtypes in African-American identify key metabolic differences

Fariba Tayyari; G A Nagana Gowda; Olufunmilayo F Olopade; Richard Berg; Howard H Yang; Maxwell P Lee; Wilfred F Ngwa; Suresh K Mittal; Daniel Raftery; Sulma I Mohammed

doi:10.18632/oncotarget.24433

Metabolic profiles of triple-negative and luminal A breast cancer subtypes in African-American identify key metabolic differences

Oncotarget. 2018 Feb 7;9(14):11677-11690. doi: 10.18632/oncotarget.24433. eCollection 2018 Feb 20.

Authors

Affiliations

¹ Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
² Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
³ The University of Chicago Medical Center, Chicago, IL 60637, USA.
⁴ Indiana University Health Arnett Medical, Lafayette, IN 47905, USA.
⁵ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁶ Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.
⁷ Depatment of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
⁸ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Abstract

Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology. In this study, we performed metabolic analysis of breast tissues to identify how TNBC differs from luminal A breast cancer (LABC) subtypes within the African-American and Caucasian breast cancer patients, respectively. We used High-Resolution Magic Angle Spinning (HR-MAS) 1H Nuclear magnetic resonance (NMR) to perform the metabolomic analysis of breast cancer and adjacent normal tissues (total n=82 samples). TNBC and LABC subtypes in African American women exhibited different metabolic profiles. Metabolic profiles of these subtypes were also distinct from those revealed in Caucasian women. TNBC in African-American women expressed higher levels of glutathione, choline, and glutamine as well as profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis concomitant with decreased levels of ATP. TNBC in Caucasian women was associated with increased pyrimidine synthesis. These metabolic alterations could potentially be exploited as novel treatment targets for TNBC.

Keywords: African American; Caucasian; NMR; breast cancer; triple-negative.