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.
Highlights
Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 25% of all cancer cases and 15% of all cancer deaths among females
A first Principal Component Analysis (PCA) analysis blindly performed on all samples identified five outliers: one patient had very high lactate plasma level probably due to inadequate blood collection or manipulation, two presented high ethanol levels and two patients showed high glucose levels due to non insulin dependent diabetes
In the field of BC, several 1H-Nuclear Magnetic Resonance (1H-NMR) based metabonomic studies compared plasma or serum metabolites profiles between EBC and metastatic BC (MBC) patients or dissected the EBC or MBC profiles themselves [9, 14] A few compared EBC patients to healthy controls [15, 16] and one study recently reported a comparative evaluation between BC and other cancer types [17]
Summary
Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 25% of all cancer cases and 15% of all cancer deaths among females. Mortality rate has declined over the last decades mainly due to advances in screening methods, leading to earlier diagnosis, and successful multidisciplinary treatments of the early diseases [1]. Metabolomics, the global qualitative and quantitative evaluation of metabolites in a biological system, by NMR spectroscopy, mass spectrometry or combined techniques [3, 4] has emerged as a unique tool to investigate the modification of metabolites of cancer cells or in biofluids and tissues of cancer patients [5, 6]. The origin of these systemic metabolic modifications remains a subject of debates. At first glance they could be considered as direct leakages of cancer cells metabolites but recent reports suggest that host response to cancer is important even at early stages [10]. The serum composition, as far as the endogenous metabolites are considered, could be remodeled due to such host-tumor interactions [7, 8, 10]
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