ORIGINAL RESEARCH

Peculiarities of amino acid profile in monocytes in breast cancer

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
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Fig. 1. Box plot of amino acids whose levels in monocytes differ significantly between the 'normal' and BC groups. The box boundaries are the first and third quartiles, the line in the middle of the box is the median; the error bars are the difference of the first quartile and the interquartile range, the sum of the third quartile and the interquartile range
Fig. 2. Result of an analysis of the metabolic pathways involving amino acids with significant differences in levels in monocytes from patients in the "normal" group and from those in the BC group. А. Analysis using the KEGG database: 1 — phenylalanine, tyrosine and tryptophan biosynthesis; 2 — glycine, serine and threonine metabolism; 3 — tryptophan metabolism; 4 — tyrosine metabolism; 5 — glyoxylate and dicarboxylate metabolism; 6 — cysteine and methionine metabolism; 7 — glutathione metabolism; 8 — arginine and proline metabolism; 9 — aminoacyl-tRNA biosynthesis. B. Analysis using the SMPDB database: 1 — aspartate metabolism; 2 — phenylalanine and tyrosine metabolism; 3 — glutathione metabolism; 4 — glycine and serine metabolism; 5 — ammonia recycling; 6 — alanine metabolism; 7 — carnitine synthesis; 8 — methionine metabolism
Fig. 3. ROC-curves of logistic regression models with monocyte amino acid levels as the independent variable and whether the sample belongs to the 'normal' or BC group as the dependent variable. The insets show the amino acids whose levels are taken as the independent variable, as well as the area under the operating curve for the corresponding logistic regression model. ROC curves are plotted for each of the statistically significantly different amino acids (A) as well as a combination of amino acids (B)
Table 1. Composition of mobile phase for LC-MS analysis of amino acids
Table 2. Transition parameters for mass spectrometric detection of amino acids
Table 3. Metabolic pathways involving amino acids with significant differences in levels in monocytes from "normal" patients and breast cancer using the KEGG database
Table 4. Metabolic pathways involving amino acids with significant differences in levels in monocytes from "normal" patients and breast cancer using the SMPDB database
Table 5. Characteristics of logistic regression models predicting BC according to the content of selected amino acids whose levels in monocytes differ significantly between the "normal" group and BC