Metabolomics Biomarkers for Breast Cancer

Günther, Ulrich L.

doi:10.1159/000430844

Cited by 68 publications

(51 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, several investigators, by using a metabolomics approach, have focused on establishing breast cancer biomarkers [38–40]. Numerous metabolites, including glucose, lactate, lipids, choline, and amino acids were shown to correlate with breast cancer [40–42]. A majority of these investigations were focused on either breast cancer tumors or cell lines.…”

Section: Discussionmentioning

confidence: 99%

1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients

et al. 2017

View full text Add to dashboard Cite

1H NMR is used to detect alterations in metabolites and their linkage to metabolic processes in a number of pathological conditions including breast cancer. Inositol 1, 4, 5 trisphosphate (IP3R) receptor is an intracellular calcium channel known to regulate metabolism and cellular bioenergetics. Its expression is up regulated in a number of cancers. However, its linkage to metabolism in disease conditions has not been evaluated. This study was designed to determine the association if any, of these metabolites with altered expression of IP3R in breast cancer. We used 1H NMR to identify metabolites in the serum of breast cancer patients (n = 27) and performed Real-time Polymerase Chain Reaction analysis for quantifying the expression of IP3R type 3 and type 2 in tissues from breast cancer patients (n = 40). Principal Component Analysis (PCA) and Partial Least Square-Discriminant Analysis (PLS-DA) clearly distinguished patients with high/low IP3R expression from healthy subjects. The present study revealed high expression of IP3R type 2 and type 3 in human breast tumor tissue compared to adjacent non-tumorous tissue. Moreover, patients with ≥ 2-fold increase in IP3R (high IP3R group) had significantly higher concentration of metabolic intermediates compared to those with < 2-fold increase in IP3R (low IP3R group). We observed an increase in lipoprotein content and the levels of metabolites like lactate, lysine and alanine and a decrease in the levels of pyruvate and glucose in serum of high IP3R group patients when compared to those in healthy subjects. Receiver operating characteristic (ROC) curve analysis was performed to show the clinical utility of metabolites. In addition to the human studies, functional relevance of IP3Rs in causing metabolic disruption was observed in MCF-7 and MDA MB-231 cells. Results from our studies bring forth the importance of metabolic (or metabolomics) profiling of serum by 1H NMR in conjunction with tissue expression studies for characterizing breast cancer patients. The results from this study provide new insights into relationship of breast cancer metabolites with IP3R.

show abstract

Section: Discussionmentioning

confidence: 99%

1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Prostaglandins, which are derived from aberrantly increased cyclooxygenase-2 (COX2) in breast tumors and which function as oncogenic lipid messengers [50–52], link breast cancer to inflammatory processes. A high ratio of glycerophosphocholine to phosphocholine (GPC/PCho) has been proposed as a marker of basal-like and luminal B breast tumors but has yielded discrepant results (reviewed in [53]). In turn, the cytidine-5-monophosphate/pentadecanoic acid ratio has been demonstrated to be a fairly reliable discriminator between cancerous and normal tissue, detecting cancer with a sensitivity of 94.8 % and a specificity of 93.9 % [54].…”

Section: Breast Tumor Metabolomementioning

confidence: 99%

“…While these marker sets vary substantially between each other, they do consistently include modifications within glycolysis parameters, phospholipid metabolism, fatty acid metabolism, and amino acid metabolism (reviewed in [53]). One study by Asiago et al [132] presented a set of 11 markers (namely formate, histidine, prolin, choline, tyrosine, 3-HB, lactate, glutamic acid, N-acetyl-glycine, 3-hydroxy-2-methyl-butanoic acid, and nonanedioic acid) being able to predict recurrent breast cancer disease with a sensitivity of 86 % and a specificity of 84 %.…”

Section: Blood-based Metabolome Analyses and Biomarkersmentioning

confidence: 99%

On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer

et al. 2016

View full text Add to dashboard Cite

Altered metabolism in tumor cells has been a focus of cancer research for as long as a century but has remained controversial and vague due to an inhomogeneous overall picture. Accumulating genomic, metabolomic, and lastly panomic data as well as bioenergetics studies of the past few years enable a more comprehensive, systems-biologic approach promoting deeper insight into tumor biology and challenging hitherto existing models of cancer bioenergetics. Presenting a compendium on breast cancer-specific metabolome analyses performed thus far, we review and compile currently known aspects of breast cancer biology into a comprehensive network, elucidating previously dissonant issues of cancer metabolism. As such, some of the aspects critically discussed in this review include the dynamic interplay or metabolic coupling between cancer (stem) cells and cancer-associated fibroblasts, the intratumoral and intertumoral heterogeneity and plasticity of cancer cell metabolism, the existence of distinct metabolic tumor compartments in need of separate yet simultaneous therapeutic targeting, the reliance of cancer cells on oxidative metabolism and mitochondrial power, and the role of pro-inflammatory, pro-tumorigenic stromal conditioning. Comprising complex breast cancer signaling networks as well as combined metabolomic and genomic data, we address metabolic consequences of mutations in tumor suppressor genes and evaluate their contribution to breast cancer predisposition in a germline setting, reasoning for distinct personalized preventive and therapeutic measures. The review closes with a discussion on central root mechanisms of tumor cell metabolism and rate-limiting steps thereof, introducing essential strategies for therapeutic targeting.

show abstract

“…However, mammography and histopathology have some limitations . Compared to traditional methods, liquid biopsies, including urine and blood, are advantageously the easiest samples to work with . Nevertheless, urine composition is highly affected by several confounding factors and prone to microbial contamination.…”

Section: Introductionmentioning

confidence: 99%

A plasma metabolite panel as biomarkers for early primary breast cancer detection

Yuan

Schafferer

Tang

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

In recent years, metabolites have attracted substantial attention as promising novel biomarkers of various diseases. However, breast cancer plasma metabolite studies are still in their infancy. Here, we investigated the potential of metabolites to serve as minimally invasive, early detection markers of primary breast cancer. We profiled metabolites extracted from the plasma of primary breast cancer patients and healthy controls using tandem mass spectrometry (UHPLC‐MS/MS and FIA‐MS/MS). Two metabolites were found to be upregulated, while 16 metabolites were downregulated in primary breast cancer patients compared to healthy controls in both the training and validation cohorts. A panel of seven metabolites was selected by LASSO regression analysis. This panel could differentiate primary breast cancer patients from healthy controls, with an AUC of 0.87 (95% CI: 0.81 ~ 0.92) in the training cohort and an AUC of 0.80 (95% CI: 0.71 ~ 0.87) in the validation cohort. These significantly differentiated metabolites are mainly involved in the amino acid metabolism and breast cancer cell growth pathways. In conclusion, using a metabolomics approach, we identified metabolites that have potential value for development of a multimarker blood‐based test to complement and improve early breast cancer detection. The panel identified herein might be part of a prescreening tool, especially for younger women or for closely observing women with certain risks, to facilitate decision making regarding which individuals should undergo further diagnostic tests. In the future, the combination of metabolites and other blood‐based molecular marker sets, such as DNA methylation, microRNA, and cell‐free DNA mutation markers, will be an attractive option.

show abstract

Metabolomics Biomarkers for Breast Cancer

Cited by 68 publications

References 63 publications

1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients

1H NMR Metabolomics Reveals Association of High Expression of Inositol 1, 4, 5 Trisphosphate Receptor and Metabolites in Breast Cancer Patients

On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer

A plasma metabolite panel as biomarkers for early primary breast cancer detection

Contact Info

Product

Resources

About