Metabolic characterization of triple negative breast cancer

BMC Cancer

Maria D Cao¹  Santosh Lamichhane⁴  Steinar Lundgren⁵  Anna Bofin²  Hans Fjøsne³  Guro F Giskeødegård¹  Tone F Bathen⁴ 

[1] St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

[2] Department of Laboratory Medicine and Children’s and Women’s Health, NTNU, Trondheim, Norway

[3] Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

[4] Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

[5] Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

关键词: Glutaminolysis;    Glycolysis;    Choline phospholipid metabolism;    Triple negative breast cancer;    HER-2 receptor;    Progesterone receptor;    Estrogen receptor;    HR MAS MRS;    Metabolomics;   

Others  :  1117902
DOI  :  10.1186/1471-2407-14-941

 received in 2014-05-09, accepted in 2014-11-25,  发布年份 2014

【 摘 要 】

Background

The aims of this study were to characterize the metabolite profiles of triple negative breast cancer (TNBC) and to investigate the metabolite profiles associated with human epidermal growth factor receptor-2/neu (HER-2) overexpression using ex vivo high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). Metabolic alterations caused by the different estrogen receptor (ER), progesterone receptor (PgR) and HER-2 receptor statuses were also examined. To investigate the metabolic differences between two distinct receptor groups, TNBC tumors were compared to tumors with ER^pos/PgR^pos/HER-2^pos status which for the sake of simplicity is called triple positive breast cancer (TPBC).

Methods

The study included 75 breast cancer patients without known distant metastases. HR MAS MRS was performed for identification and quantification of the metabolite content in the tumors. Multivariate partial least squares discriminant analysis (PLS-DA) modeling and relative metabolite quantification were used to analyze the MR data.

Results

Choline levels were found to be higher in TNBC compared to TPBC tumors, possibly related to cell proliferation and oncogenic signaling. In addition, TNBC tumors contain a lower level of Glutamine and a higher level of Glutamate compared to TPBC tumors, which indicate an increase in glutaminolysis metabolism. The development of glutamine dependent cell growth or “Glutamine addiction” has been suggested as a new therapeutic target in cancer. Our results show that the metabolite profiles associated with HER-2 overexpression may affect the metabolic characterization of TNBC. High Glycine levels were found in HER-2^pos tumors, which support Glycine as potential marker for tumor aggressiveness.

Conclusions

Metabolic alterations caused by the individual and combined receptors involved in breast cancer progression can provide a better understanding of the biochemical changes underlying the different breast cancer subtypes. Studies are needed to validate the potential of metabolic markers as targets for personalized treatment of breast cancer subtypes.

【 授权许可】

   
2014 Cao et al.; licensee BioMed Central Ltd.

【 图 表 】

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