Tumor-dependent increase of serum amino acid levels in breast cancer patients has diagnostic potential and correlates with molecular tumor subtypes

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.

In vitro quantitative analysis of Salmonella typhimurium preference for amino acids secreted by human breast tumor

“…In order to verify a chemotactic preference of S. typhimurium when exposed the multiple cancer secreting amino acids, the reference values of amino acid concentration in serum from breast cancer patients and healthy donors were investigated [13]. Among these amino acids, the aspartate, the serine, and the alanine were chosen, which have lowest values of the threshold concentration (concentration of attractant that induces an accumulation of bacteria in the capillary significantly greater than that obtained absence of attractant) as previous studies showed [31].…”

“…Among these amino acids, the aspartate, the serine, and the alanine were chosen, which have lowest values of the threshold concentration (concentration of attractant that induces an accumulation of bacteria in the capillary significantly greater than that obtained absence of attractant) as previous studies showed [31]. Table 1 shows the reference values of threshold concentration of amino acid [31] and secreted concentration from health donors and breast cancer patients [13].…”

“…One of the possible mechanisms is the positive chemotaxis toward amino acids released from tumors. Tumors are known to possess and release the high concentration of amino acids, such as aspartate, serine, alanine, glutamine, glutamate, and etc., compared with the surrounding normal tissues [13].…”

Influence of dietary fats on circulating amino acid profile in experimental breast cancer

“…In fact, there are many studies focused on the role of circulating free amino acids as biomarkers of alterations in protein metabolism associated with cancer [30,31]. In addition, the description of different amino acid profiles for specific types of cancer has suggested that the metabolic alterations of each type of tumor determine its own plasma amino acid profile; therefore, the possibility that each type of cancer can promote specific amino acid profile has suggested the important role of amino acids in the diagnosis of this pathology [6,[11][12][13]15,16,32,33].…”

“…Therefore, the circulating free amino acids profile may be altered and reflect the onset and development of the tumor [10]. In the last years, many researchers have demonstrated an increased interest in blood free amino acid profile and their potential use as biomarkers of cancer and other pathologies [11][12][13][14][15]. Earlier studies showed that plasma amino acid levels alteration in cancer patients were closely related to cachexia and weight loss [16,17].…”