Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery

Abstract

Breast cancer is the most common cancer in women worldwide, and the development of new technologies for better understanding of the molecular changes involved in breast cancer progression is essential. Metabolic changes precede overt phenotypic changes, because cellular regulation ultimately affects the use of small-molecule substrates for cell division, growth or environmental changes such as hypoxia. Differences in metabolism between normal cells and cancer cells have been identified. Because small alterations in enzyme concentrations or activities can cause large changes in overall metabolite levels, the metabolome can be regarded as the amplified output of a biological system. The metabolome coverage in human breast cancer tissues can be maximized by combining different technologies for metabolic profiling. Researchers are investigating alterations in the steady state concentrations of metabolites that reflect amplified changes in genetic control of metabolism. Metabolomic results can be used to classify breast cancer on the basis of tumor biology, to identify new prognostic and predictive markers and to discover new targets for future therapeutic interventions. Here, we examine recent results, including those from the European FP7 project METAcancer consortium, that show that integrated metabolomic analyses can provide information on the stage, subtype and grade of breast tumors and give mechanistic insights. We predict an intensified use of metabolomic screens in clinical and preclinical studies focusing on the onset and progression of tumor development.

Extensive Decoupling of Metabolic Genes in Cancer

“…A particularly interesting kidney-specific gene was DPEP1 (a dipeptidase) in light of the recently observation of elevated dipeptide levels in a subset of clear cell renal carcinoma tumors (manuscript in preparation). In contrast, breast-specific genes included CDO1 (cysteine dioxygenase Type 1, whose inactivation was recently reported to contribute to survival and drug resistance in breast cancer [27]) and a number of genes involved in glycerolipid/lipid biosynthesis and associated with malignancy in breast cancer (GPAM [15] and MGLL [37]).…”

Glutamate enrichment as new diagnostic opportunity in breast cancer

“…However, we and other have shown that mass spectrometry based metabolomics using fresh-frozen tissue samples is feasible and reproducible. [28][29][30][31] Because patient age represents a potentially cofounding factor, we carried out a comparing analysis of older (>50 years) versus younger patients (50 years). Only three metabolites were found to be significantly changed in the TS and could be validated in the VS: urea (fold change 5 1.6), pseudo uridine (fold change 5 1.2) and guanosine (fold change 5 21.3).…”

Review: Toxicometabolomics

“…Metabolomics analysis of samples from patients have identified promising biomarkers that can be used to detect several kinds of cancers such as bladder (Cao et al, 2012;Jobu et al, 2012), colorectal (Nishiumi et al, 2012), breast (Slupsky et al, 2010), ovarian (Garcia et al, 2011;Slupsky et al, 2010;), kidney (Ganti and Weiss, 2011;Lin et al, 2011b), liver (Chen et al, 2011b) and lung cancer . In addition, metabolomics has been useful in cancer research for therapeutic evaluations (Chung et al, 2003;Tenori et al, 2012) and in mechanistic understanding (Adinolfi et al, 2012;Denkert et al, 2012;Klawitter et al, 2011).…”