Abstract
BackgroundMalignancies induce changes in the levels of serum amino acids (AA), which may offer diagnostic potential. Furthermore, changes in AA levels are associated with immune cell function. In this study, serum AA levels were studied in breast cancer patients versus patients with benign breast lesions.MethodsIn a prospective study, serum levels of 15 AA were measured by high performance liquid chromatography before and after surgery in 41 breast cancer patients (BrCA) and nine patients with benign breast lesions (healthy donors, HD). Results were analyzed in relation to clinical tumor data and tested against immunological flow cytometry data. Principal component analysis was performed and the accuracy of AA levels as a potential diagnostic tool was tested.ResultsPre- but not postoperative serum AA levels were increased in BrCA in eight out of 15 AA compared with HD. Serum AA levels were highest in the most aggressive (basal-like) as compared with the least aggressive tumor subtype (luminal A). A principal component (PC1) of all measured AA correlated with a mainly pro-inflammatory immune profile, while a second one (PC2, selectively considering AA preoperatively differing between HD and BrCA) could predict health state with an area under the curve of 0.870.ConclusionsBreast cancer shows a tumor-dependent impact on serum AA levels, which varies with intrinsic tumor subtypes and is associated with a pro-inflammatory state. Serum AA levels need further evaluation as a potential diagnostic tool.
Highlights
Amino acids (AA) are an integral part of most metabolomics analysis
We have previously shown that T lymphocytes in the blood, lymph nodes and tumor of the present breast cancer patient cohort expressed decreased levels of the TCR-zeta chain, which is essential for the transduction of stimulatory signals [11]
Miyagi et al could show an increase in the plasma free amino acids threonine, serine, proline, glycine, alanine, ornithine and lysine, and a decrease of glutamine, tyrosine, histidine and tryptophane in 196 breast cancer patients in comparison with 976 controls [4]
Summary
Amino acids (AA) are an integral part of most metabolomics analysis. As metabolomics measure downstream output rather than upstream gene and protein products, they offer the opportunity of an integrated evaluation of multiple pathways and their biological consequences [1]. Building on the Warburg effect [6], the metabolic shift in tumor cells from respiration to fermentation should result in an increased demand for and consumption of amino acids, amongst other substances. This has been shown by several publications [7,8]. An amino acid-rich substrate could inhibit tumor growth by cell cycle arrest and initiation of apoptosis in a murine model [9] These contradictory findings may well represent a dose-dependent effect, rendering both the “depletion” and the “overload” model valid. Serum AA levels were studied in breast cancer patients versus patients with benign breast lesions
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