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Simple Summary: It was shown for the first time that the salivary levels of the MUC1 family, including CA 15-3, CA 27.29, and MCA, were significantly dependent on the expression of human epidermal growth factor receptor 2 (HER2) in breast cancer patients. In the presence of HER2 expression, mucin levels decreased with a simultaneous decrease in the levels of free estrogen and progesterone and an increase in the content of pro-inflammatory cytokines and free amino acids, which was consistent with the aggressive growth pattern and high invasiveness of HER2-positive breast cancer subtypes. The MUC1 family of transmembrane glycoproteins (CA 15-3, CA 27.29, MCA) is aberrantly expressed among patients with breast cancer. Objectives: to measure the level of degradation products of MUC1, including CA 15-3, CA 27.29, and MCA, in the saliva of breast cancer patients and to describe the biochemical processes that influence their expression and the regulation of their biological functions. Methods: The case–control study included three groups (breast cancer, fibroadenomas, and healthy controls). All study participants provided saliva samples strictly before starting treatment. The levels of MUC1, including CA 15-3, CA 27.29, and MCA, free progesterone and estradiol, cytokines (MCP-1, VEGF, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18), and amino acids (Asp, Gln, Gly, His, Leu + Ile, Orn, Phe, Pro, Tyr) were determined. Results: It was shown that the levels of the MUC1 family in the saliva of patients with HER2-positive breast cancer were significantly lower compared to the control group. The level of pro-inflammatory cytokines and the level of free estradiol affected the expression of MUC1. We obtained a reliable relationship between the aggressive nature of tumor growth, an increased level of pro-inflammatory cytokines, a low level of free estradiol, and the suppressed expression of salivary MUC1. Conclusions: Among patients with aggressive breast cancer, a high level of pro-inflammatory cytokines, and a low level of free estradiol, there was an inhibition of the expression of pathologically unchanged glycoprotein MUC1 in saliva. [ABSTRACT FROM AUTHOR]

This study of the features of the biochemical composition of biological fluids in patients with breast cancer, including saliva, allows us to identify some indicators as metabolic predictors of the presence of the disease. Objectives: to study the influence of the menopause factor and body mass index (BMI) on the biochemical composition of saliva and to evaluate the applicability of metabolic markers of saliva for the diagnosis of breast cancer. Methods: The case–control study involved 1438 people (breast cancer, n = 543; fibroadenomas, n = 597; control, n = 298). A comprehensive study of the biochemical composition of saliva was carried out using 36 parameters. Results: When comparing the salivary biochemical composition in breast cancer, fibroadenomas, and controls, it is necessary to take into account the menopausal status, as well as BMI (less than 25 or more) for the group of patients with preserved menstrual function. A complex of biochemical parameters has been identified that change in saliva during breast cancer, regardless of menopause and BMI (total protein, urea, uric acid, NO, α-amino acids, GGT), as well as specific parameters that must be taken into account when analyzing individual subgroups (imidazole compounds, LDH, catalase, α-amylase). During the study of a separate group of patients with leaf-shaped (phyllodes) tumors, we found similarities with breast cancer in the changes in some biochemical parameters that can be attributed to metabolites of malignant growth (protein, α-amino acids, calcium, NO, pyruvate, peroxidase, α-amylase). Conclusions: We demonstrated changes in a wide range of salivary biochemical parameters depending on the presence of fibroadenomas and breast cancer. From the point of view of clinical practice, this may be useful information for monitoring the condition of patients with fibroadenomas, which are difficult to unambiguously classify based on instrumental diagnostics alone. [ABSTRACT FROM AUTHOR]

In this work, we focused on the analysis of VEGF content in saliva and its relationship with pro-inflammatory cytokines and amino acids involved in immunomodulation and angiogenesis in breast cancer. The study included 230 breast cancer patients, 92 patients with benign breast disease, and 59 healthy controls. Before treatment, saliva samples were obtained from all participants, and the content of VEGF and cytokines in saliva was determined by an enzyme-linked immunosorbent assay, as well as the content of amino acids by high-performance liquid chromatography. It was found that VEGF was positively correlated with the level of pro-inflammatory cytokines IL-1β (r = 0.6367), IL-6 (r = 0.3813), IL-8 (r = 0.4370), and IL-18 (r = 0.4184). Weak correlations were shown for MCP-1 (r = 0.2663) and TNF-α (r = 0.2817). For the first time, we demonstrated changes in the concentration of VEGF and related cytokines in saliva in different molecular biological subtypes of breast cancer depending on the stage of the disease, differentiation, proliferation, and metastasis to the lymph nodes. A correlation was established between the expression of VEGF and the content of aspartic acid (r = −0.3050), citrulline (r = −0.2914), and tryptophan (r = 0.3382) in saliva. It has been suggested that aspartic acid and citrulline influence the expression of VEGF via the synthesis of the signaling molecule NO, and then tryptophan ensures tolerance of the immune system to tumor cells. [ABSTRACT FROM AUTHOR]

Changes in the concentration of tryptophan (Trp) indicate a serious metabolic restructuring, which is both a cause and a consequence of many diseases. This work examines the upward change in salivary Trp concentrations among patients with breast cancer. This study involved volunteers divided into three groups: breast cancer (n = 104), non-malignant breast pathologies (n = 30) and healthy controls (n = 20). In all participants, before treatment, the quantitative content of Trp in saliva was determined by capillary electrophoresis. In 20 patients with breast cancer, Trp was re-tested four weeks after surgical removal of the tumor. An increase in the Trp content in saliva in breast cancer has been shown, which statistically significantly decreases after surgical removal of the tumor. A direct correlation was found between increased Trp levels with the degree of malignancy and aggressive molecular subtypes of breast cancer, namely triple negative and luminal B-like HER2-negative. These conclusions were based on an increase in Ki-67 and an increase in Trp in HER2-negative and progesterone-negative subtypes. Factors under which an increase in Trp concentration in saliva was observed were identified: advanced stage of breast cancer, the presence of regional metastasis, low tumor differentiation, a lack of expression of HER2, estrogen and progesterone receptors and the high proliferative activity of the tumor. Thus, the determination of salivary Trp may be a valuable tool in the study of metabolic changes associated with cancer, particularly breast cancer. [ABSTRACT FROM AUTHOR]

Currently, the antioxidant properties of amino acids and their role in the physicochemical processes accompanying oxidative stress in cancer remain unclear. Cancer cells are known to extensively uptake amino acids, which are used as an energy source, antioxidant precursors that reduce oxidative stress in cancer, and as regulators of inhibiting or inducing tumor cell-associated gene expression. This review examines nine amino acids (Cys, His, Phe, Met, Trp, Tyr, Pro, Arg, Lys), which play a key role in the non-enzymatic oxidative process in various cancers. Conventionally, these amino acids can be divided into two groups, in one of which the activity increases (Cys, Phe, Met, Pro, Arg, Lys) in cancer, and in the other, it decreases (His, Trp, Tyr). The review examines changes in the metabolism of nine amino acids in eleven types of oncology. We have identified the main nonspecific mechanisms of changes in the metabolic activity of amino acids, and described direct and indirect effects on the redox homeostasis of cells. In the future, this will help to understand better the nature of life of a cancer cell and identify therapeutic targets more effectively. [ABSTRACT FROM AUTHOR]

Saliva is a promising biological fluid for the diagnosis and monitoring of diseases, including breast cancer. To study the composition of saliva, a complex of "omics" technologies is used: genomics, transcriptomics, proteomics, metabolomics and microbiomics. In this review, we systematized all known "omics" in their application to saliva analysis in breast cancer in order to understand how complete the picture is provided by the combination of different areas of research and to identify missing links. It has been shown that studies of saliva in breast cancer are chaotic and unsystematic. Inconsistency of sample sizes and high heterogeneity of breast cancer were identified. The main tasks that need to be solved for the complete and harmonious development of salivaomics in a new direction-"salivaonkoomics" are formulated. Thus, it is necessary to systematize and unify the study of biomarkers within each area of "omics", including sample size and its homogeneity, a list of methods and approaches, a list of biomarkers, reproducibility of results, and the ability to transfer results to other samples. It is important to expand the number of components of "omics" by adding new methods (for example, spectralomics, etc.), as well as studying the relationships between different "omics" technologies (interactomics). All this together will allow the study of saliva not only in breast cancer but also in many other pathologies to a qualitatively new level., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Currently, the antioxidant properties of amino acids and their role in the physicochemical processes accompanying oxidative stress in cancer remain unclear. Cancer cells are known to extensively uptake amino acids, which are used as an energy source, antioxidant precursors that reduce oxidative stress in cancer, and as regulators of inhibiting or inducing tumor cell-associated gene expression. This review examines nine amino acids (Cys, His, Phe, Met, Trp, Tyr, Pro, Arg, Lys), which play a key role in the non-enzymatic oxidative process in various cancers. Conventionally, these amino acids can be divided into two groups, in one of which the activity increases (Cys, Phe, Met, Pro, Arg, Lys) in cancer, and in the other, it decreases (His, Trp, Tyr). The review examines changes in the metabolism of nine amino acids in eleven types of oncology. We have identified the main nonspecific mechanisms of changes in the metabolic activity of amino acids, and described direct and indirect effects on the redox homeostasis of cells. In the future, this will help to understand better the nature of life of a cancer cell and identify therapeutic targets more effectively.