«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer

Abstract

The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 patients with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients strictly before the start of treatment and the values of 42 biochemical indicators were determined. It has been established that the saliva of healthy volunteers and patients with various molecular biological subtypes of breast cancer differs in 12 biochemical indicators: concentrations of protein, urea, nitric oxide, malondialdehyde, total amino acid content, and activity of lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, catalase, amylase, superoxide dismutase, and peroxidases. The saliva composition of patients with basal-like breast cancer differs from other subtypes in terms of the maximum number of indicators. Changes in biochemical indicators indicated an increase in the processes of lipid peroxidation and endogenous intoxication and a weakening of antioxidant protection, which correlates with the severity of the disease and the least favorable prognosis for this subtype of breast cancer. An analysis was made of the individual contribution of the expression level of HER2, estrogen, and progesterone receptors to changes in the biochemical composition of saliva. The HER2 (-)/HER2 (+) group, which should be considered as a single group, as well as ER-positive breast cancer, differ statistically significantly from the control group. For ER/PR-positive breast cancer, a more favorable ratio of saliva biochemical indicators was also noted compared to ER/PR-negative breast cancer.

Keywords: HER2 status; biomarkers; breast cancer; estrogen receptors; molecular biological subtype; progesterone receptors; saliva; salivaomics.

Figure 1

Individuals factor map (PCA) with control group (A) and without control group (C); variables factor map with control group (B) and without control group (D). LDH—lactate dehydrogenase, CAT—catalase, ALP—alkali phosphatase, AST—aspartate aminotransferase, MDA—malondialdehyde, GGT—gamma glutamyltransferase, α-AA—α-Amino acids, SB—Schiff Bases, TC—triene conjugates, DC—diene conjugates, SOD—superoxide dismutase.

Figure 2

Biochemical composition of saliva depending on the molecular biological subtype of breast cancer. Differences between groups were calculated using the Wilcoxon matched pairs test with the Bonferoni correction at p < 0.05; *—differences with the control group are statistically significant, **—differences with BL are statistically significant. C—concentration, A—activity.

Figure 3

Individual factor map (PCA) with control group (A) and without control group (C); variables factor map with control group (B) and without control group (D). UA—uric acid, LDH—lactate dehydrogenase, CAT—catalase, ALP—alkali phosphatase, ALT—alanine aminotransferase, AST—aspartate aminotransferase, MDA—malondialdehyde, GGT—gamma glutamyltransferase, α-AA—α-Amino acids, SOD—superoxide dismutase.

Figure 4

Relative change in biochemical indicators of saliva depending on the status of HER2 receptors. The interval of variation is given in comparison with the control group. The numbers of biochemical indicators correspond to the serial number in Table 2 and Table 3. *—differences between groups with HER2-positive and HER2-negative status are statistically significant, p < 0.05.

Figure 5

Individuals factor map (PCA) with control group (A) and without control group (C); variables factor map with control group (B) and without control group (D). UA—uric acid, LDH—lactate dehydrogenase, CAT—catalase, ALP—alkali phosphatase, MDA—malondialdehyde, SB—Schiff Bases, TC—triene conjugates, GGT—gamma glutamyltransferase, α-AA—α-Amino acids, P—phosphorus, MM—middle molecules.

Figure 6

Relative change in biochemical indicators of saliva depending on the status of ER receptors. The interval of variation is given in comparison with the control group. The numbers of biochemical indicators correspond to the serial number in Table 2 and Table 3. *—differences between groups with ER-positive and ER-negative status are statistically significant, p < 0.05.

Figure 7

Individuals factor map (PCA) with control group (A) and without control group (C); variables factor map with control group (B) and without control group (D). UA—uric acid, LDH—lactate dehydrogenase, CAT—catalase, ALP—alkali phosphatase, ALT—alanine aminotransferase, AST—aspartate aminotransferase, MDA—malondialdehyde, GGT—gamma glutamyltransferase, α-AA—α-Amino acids, SOD—superoxide dismutase, SM—seromucoids.

Figure 8

Relative change in biochemical indicators of saliva depending on the status of PR receptors. The interval of variation is given in comparison with the control group. The numbers of biochemical indicators correspond to the serial number in Table 2 and Table 3. *—differences between groups with PR-positive and PR-negative status are statistically significant, p < 0.05.