Free Salivary Amino Acid Profile in Breast Cancer: Clinicopathological and Molecular Biological Features.

The study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular biological subtypes of breast cancer to obtain a more complete picture and evaluate the potential utility of individual amino acids or their combinations for diagnostic purposes. This study included 116 patients with breast cancer, 24 patients with benign breast disease, and 25 healthy controls. From all patients, strictly before the start of treatment, saliva samples were collected, and the quantitative content of 26 amino acids was determined. Statistically significant differences between the three groups are shown in the content of Asp, Gly, Leu + Ile, Orn, Phe, Pro, Thr, and Tyr. To differentiate the three groups from each other, a decision tree was built. To construct it, we selected those amino acids for which the change in concentrations in the subgroups was multidirectional (GABA, Hyl, Arg, His, Pro, and Car). For the first time, it is shown that the amino acid profile of saliva depends on the molecular biological subtype of breast cancer. The most significant differences are shown for the luminal B HER2-positive and TNBC subgroups. In our opinion, it is critically important to consider the molecular biological subtype of breast cancer when searching for potential diagnostic markers.

The Role of Amino Acids in the Diagnosis, Risk Assessment, and Treatment of Breast Cancer: A Review.

This review summarizes the role of amino acids in the diagnosis, risk assessment, imaging, and treatment of breast cancer. It was shown that the content of individual amino acids changes in breast cancer by an average of 10-15% compared with healthy controls. For some amino acids (Thr, Arg, Met, and Ser), an increase in concentration is more often observed in breast cancer, and for others, a decrease is observed (Asp, Pro, Trp, and His). The accuracy of diagnostics using individual amino acids is low and increases when a number of amino acids are combined with each other or with other metabolites. Gln/Glu, Asp, Arg, Leu/Ile, Lys, and Orn have the greatest significance in assessing the risk of breast cancer. The variability in the amino acid composition of biological fluids was shown to depend on the breast cancer phenotype, as well as the age, race, and menopausal status of patients. In general, the analysis of changes in the amino acid metabolism in breast cancer is a promising strategy not only for diagnosis, but also for developing new therapeutic agents, monitoring the treatment process, correcting complications after treatment, and evaluating survival rates.

Metabolic Features of Saliva in Breast Cancer Patients.

The aim of the work was to study the metabolic characteristics of saliva in breast cancer and the subsequent assessment of the potential information content of its individual biochemical indicators. The study included 487 patients of the Omsk Clinical Oncology Center with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients before the start of treatment, and the values of 34 biochemical indicators were determined. It has been shown that concentration of total protein, urea, uric acid (UA), the total content of α-amino acids and lipid peroxidation products, and the activity of metabolic and antioxidant enzymes (in particular catalase-CAT) of saliva changed significantly in breast cancer. Biochemical indicators characterizing early breast cancer have been identified, which can be used for timely diagnosis in addition to existing methods. The coefficients UA/Urea and UA·CAT/Urea are proposed, for which the maximum deviation from the norm was observed in the early stages of the disease. It was shown that for ductal breast cancer, changes in the activity of metabolic enzymes of saliva were more pronounced, while, for lobular breast cancer, the indicators of enzymatic and non-enzymatic components of antioxidant protection changed. The results confirmed the potential importance of saliva in the diagnosis of breast cancer.

Application of FTIR Spectroscopy for Quantitative Analysis of Blood Serum: A Preliminary Study.

The aim of this study was to analyze the possibility of simultaneous determination of the concentration of components from the characteristics of FTIR spectra using the example of a model blood serum. To prepare model solutions, a set of freeze-dried control sera based on bovine blood serum was used, certified for approximately 38 parameters. Based on the values of the absorbance and areas of absorption bands in the FTIR spectra of model solutions, a regression equation was constructed by solving a nonlinear problem using the generalized reduced gradient method. By using the absorbance of the absorption bands at 1717 and 3903 cm-1 and the areas of the absorption bands at 616, 3750, and 3903 cm-1, it is possible to simultaneously determine the concentrations of 38 components with an error of less than 0.1%. The results obtained confirm the potential clinical use of FTIR spectroscopy as a reagent-free express method for the analysis of blood serum. However, its practical implementation requires additional research, in particular, analysis of real blood serum samples and validation of the method.

Features of the Metabolic Profile of Saliva in Lung Cancer and COPD: The Effect of Smoking Status.

The aim of the study was to compare the metabolic characteristics of the salivary composition in lung cancer, chronic obstructive pulmonary disease (COPD) and their combination, depending on the smoking history. The study group included 392 patients with lung cancer of various histological types. The division into subgroups was carried out in accordance with the severity of COPD and smoking experience. Salivary biochemical composition was determined according to 34 indicators. For data processing, the principal component method was used. Different groups of biochemical saliva markers are informative when separately accounting for the smoking factor and the presence of COPD in lung cancer. For smoking, antioxidant enzymes and electrolyte components of saliva are informative; for COPD metabolic enzymes, lipid peroxidation products, sialic acids and electrolyte components are informative. While taking into account the smoking factor and the presence of COPD, biochemical markers corresponding to the presence/absence and severity of COPD are the priority. Changes occurring in the background of smoking are of a secondary nature, manifesting as much as possible with a smoking history of more than 50 pack-years. Thus, the metabolic changes that occur in lung cancer in combination with COPD, depending on the smoking factor, can be estimated using saliva.

Age and Gender Characteristics of the Infrared Spectra of Normal Human Saliva.

The comparison of the characteristics of the infrared (IR) spectra of saliva of healthy volunteers was carried out based on gender and age. It is shown that statistically significant differences between male and female groups are observed for the absorption bands of proteins and lipids. At the same time, the absorbance of the bands assigned to proteins and nucleic acids is higher for males, whereas the absorbance of the bands assigned to lipids is higher in the group of females. It is established that the correlation relationships of the characteristics of the spectra and age are weakly expressed. Thus, when forming the criteria of the norm and pathology for saliva, it is necessary to take into account the gender of the subjects, while there are no strict requirements for taking into account age periodization. Nevertheless, the revealed patterns are valid only for the composition of the saliva of healthy volunteers, the extension of the results to groups of patients with various diseases, as well as other biological fluids, requires additional testing.

Salivary Metabolic Profile of Patients with Lung Cancer, Chronic Obstructive Pulmonary Disease of Varying Severity and Their Comorbidity: A Preliminary Study.

The aim of the work was to study the features of the salivary biochemical composition in the combined pathology of lung cancer and chronic obstructive pulmonary disease (COPD) of varying severity (COPD I, COPD II). The study group included patients with lung cancer (n = 392), non-malignant lung pathologies (n = 168) and healthy volunteers (n = 500). Before treatment, the salivary biochemical composition was determined according to 34 indicators. Survival analysis performed by the Kaplan-Meier method. Biochemical parameters (catalase, imidazole compounds ICs, sialic acids, lactate dehydrogenase (LDH)) that can be used to monitor patients at risk (COPD I) for timely diagnosis of lung cancer are determined. A complex of salivary biochemical indicators with prognostic value in lung cancer was revealed. For patients with lung cancer without COPD, a group of patients with a favorable prognosis can be distinguished with a combination of ICs < 0.478 mmol/L and LDH >1248 U/L (HR = 1.56, 95% CI 0.40-6.07, p = 0.03891). For COPD I, a level of ICs < 0.182 mmol/L are prognostically favorable (HR = 1.74, 95% CI 0.71-4.21, p = 0.07270). For COPD II, combinations of pH < 6.74 and LDH >1006 U/L are prognostically favorable. In general, for patients with lung cancer in combination with COPD I, the prognosis is more favorable than without COPD.

Diagnostic and Prognostic Value of Salivary Biochemical Markers in Oral Squamous Cell Carcinoma.

The purpose of the work is a comprehensive assessment of biochemical saliva markers for the diagnosis and prognosis of oral cancer. The group of patients included 68 patients with oral squamous cell carcinoma, 50 with non-cancerous diseases of the oral cavity, and 114 healthy volunteers. Before the start of treatment, 23 biochemical parameters of saliva were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 and R package. A complex of metabolic changes occurring in saliva in oral cancer is described. It was shown that none of the studied parameters could be used to diagnose oral cancer in an independent variant; the use of combinations of parameters is more informative. The high prognostic value of the content of malondialdehyde (MDA) and the Na/K-ratio in saliva before treatment was established. Thus, the content of MDA ˂ 7.34 nmol/mL and the Na/K-ratio > 1.09 c.u. is a prognostically unfavorable factor (HR = 7.88, 95% CI 1.10-54.62, p = 0.01876), which may be useful for optimizing the treatment of patients with oral cancer. It has been shown that saliva has great potential for the development of diagnostic and prognostic tests for oral cancer.