Peculiarities of amino acid profile in monocytes in breast cancer

Novoselova AV1, Yushina MN1, Patysheva MR2,3, Prostakishina EA1, Bragina OD2, Garbukov EYu2, Kzhyshkowska JG3,4,5,6
About authors

1 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia

2 Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russia

3 Tomsk National State University, Tomsk, Russia

4 Siberian State Medical University, Tomsk, Russia

5 Institute of Transfusion Medicine and Immunology, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany

6 German Red Cross Blood Service Baden-Württemberg-Hesse, Mannheim, Germany

Correspondence should be addressed: Anastasia V. Novoselova
Academik Oparin street, 4, Moscow, 117198, Russia; moc.liamg@hciveknarfv

About paper

Funding: The study was financially supported by the Russian Federation represented by the Ministry of Science and Higher Education of the Russian Federation (agreement dated 29 September 2021 № 075-15-2021-1073 on the topic "Genetic and epigenetic editing of tumor cells and the microenvironment in order to block metastasis ").

Author contribution: Novoselova АV — material processing, monocyte amino acid profile analysis, statistical data processing, text editing; Yushina MN — material processing, text writing and editing; Patysheva MR — study concept and design, monocyte isolation; Prostakishina EA — monocyte isolation; Bragina OD, Garbukov EY — patient selection, collection of biological material; Kzhyshkowska JG — study concept and design.

Compliance with ethical standards: the study is approved by the ethics committee of the Research Institute of Oncology under Tomsk National Research Medical Center (record No.10 dated 05 December 2019), was conducted in accordance with the standards of the ethics committee of V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, federal laws of the Russian Federation (Nos. 152, 323, etc.) and the 1964 Declaration of Helsinki with all subsequent additions and amendments regulating scientific research on biomaterials obtained from humans. All participants signed an informed consent to participate in the study.

Received: 2022-12-08 Accepted: 2022-12-22 Published online: 2022-12-28

Monocytes are large circulating white blood cells that are the main precursors of tissue macrophages as well as tumor-associated macrophages in the adult body. Different types of monocytes have multidirectional effects on the growth and metastatic spread of cancer cells, both activating and inhibiting these processes. Tumor progression is associated with the triggering of a whole cascade of inflammatory and immune reactions. These pathological processes are associated with changes in the amino acid content of monocytes, which can lead to disruption of their function, in particular their migration, division and maturation. The aim of the work was to profile the amino acids of monocytes, followed by a study of the amino acid composition of monocytes from patients with breast cancer using liquid chromatography with mass spectrometric detection. Significant differences in metabolite levels in monocytes of breast cancer patients and monocytes of healthy donors were found for glycine (p-value = 0.0127), asparagine (p-value = 0.0197), proline (p-value = 0.0159), methionine (p-value = 0.0357), tryptophan (p-value = 0.0028), tyrosine (p-value = 0.0127). In the study, we identified biological networks that could potentially be involved in altering the phenotype of monocytes affected by breast cancer (BC), using bioinformatic analysis of metabolic pathways involving the discovered amino acids. Mathematical models based on amino acid combinations with 100% sensitivity and specificity have been developed. Features of immune system cell metabolism in BC have been identified and potential diagnostic biomarkers have been proposed.