Does the 1H-NMR plasma metabolome reflect the host-tumor interactions in human breast cancer?

Abstract

Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters. In particular lactate levels are inversely correlated with the tumor size in the EBC cohort (Pearson correlation r = −0.309; p = 0.044). We suggest that, in BC patients, tumor cells could induce modulation of the whole patient's metabolism even at early stages. If confirmed in a lager study these observations could be of clinical importance.

NMR‐based metabolomics of biofluids in cancer

“…Here, an orthogonalized partial least squares discriminant analysis model was built using data from 85 patients and validated in a cohort of 112 patients. A metabolic profile consisting of nine discriminant metabolites was established, but this profile was remarkably different from the one described by Richard et al The two studies had only one discriminant metabolite in common (pyruvate), but were in disagreement with respect to the level of pyruvate in metastatic versus early disease.…”

“…In BCa, for example, the plasma metabolome has been found to discriminate between early‐stage and metastatic disease . Among the most important discriminant metabolites were lactate, glucose, and pyruvate.…”

“…As metabolite concentrations are regulated by numerous homeostatic mechanisms in the body, it may be challenging to relate metabolic profiles directly to cancer cell metabolism. As an example, serum lactate levels do not scale directly with tumor burden despite the fact that most tumors excrete this metabolite in large amounts . Nevertheless, several recent studies suggest that biofluid metabolomics can provide information about cancer phenotype, grade, and stage, and has potential as a clinical tool for cancer diagnostics, prognostics, and treatment monitoring.…”

Effect of Estrogen Receptor Status on Circulatory Immune and Metabolomics Profiles of HER2-Positive Breast Cancer Patients Enrolled for Neoadjuvant Targeted Chemotherapy

“…Metabolomics is a relatively new -omics approach useful to study the complex and dynamic biochemical interplay occurring between cancer and host [13]. Thus, metabolomics not only can potentially identify the biochemical signals directly caused by the presence of cancer, but it can also detect the interaction between cancer and host, which is mainly mediated by the immune system.…”

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

“…A significant part of this gluconeogenic glutamine comes from catabolism of muscle proteins, which reflects the correlation between cachexia and gluconeogenesis . Very recently, a study of plasma metabolome from breast cancer patients revealed a positive correlation between lactate, pyruvate, and alanine levels, and a negative correlation of pyruvate and alanine with glucose . This corresponds with the Cori cycle, an inter‐system cycle active in tumor patients: lactate released from cancer cells, but also from muscles, goes to the liver, as well as alanine from muscle, and these metabolites are used in gluconeogenesis in that organ, increasing the glucose available for cancer cells and their stroma, and thus enhancing tumor malignancy and associated body weight loss (Figure ) .…”