Investigação de soro e saliva por espectroscopia ATR-FTIR e avaliação de biomarcadores inflamatórios sistêmicos como estratégia de análise do câncer de mama

Abstract

Introduction: Breast cancer is the most common malignant neoplasm among women worldwide and represents a significant public health challenge due to its molecular heterogeneity and prognostic impact. Therefore, the search for non-invasive and cost-effective methods of diagnosis and prognostic stratification becomes essential. Objective: To evaluate the clinical applicability of complementary approaches for the diagnosis and prognosis of breast cancer, investigating the usefulness of profiles obtained from biological fluids and systemic inflammatory and immunological biomarkers, as well as their correlations with clinicopathological characteristics and overall survival of women with breast cancer, including advanced cases. Materials and methods: In the first article, a cross-sectional study was conducted involving 73 participants: 31 with breast cancer, 18 with benign breast disease, and 24 healthy controls. Serum and saliva samples were analyzed by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), and spectral differences between groups were statistically evaluated. In the second article, a prospective study was conducted with 33 patients with advanced breast cancer followed in a palliative care program in Brazil between 2021 and 2024. Systemic inflammatory biomarkers were quantified by blood count and enzyme-linked immunosorbent assay (ELISA), and correlated with overall survival using Kaplan-Meier analyses and Cox regression models. Results: In the first article, the intragroup spectral analysis between breast cancer and benign breast disease, serum spectra showed no statistical differences. In saliva, only the peak at 2930 cm⁻¹, associated with C–H stretching vibration of lipids, differentiated breast cancer from benign breast disease (p = 0.0391). In the comparison between breast cancer and healthy controls, serum showed a significant difference at 1295 cm⁻¹ (related to nucleic acid cytokines). Saliva showed significant differences at 1241 cm⁻¹ (nucleic acid phosphate), 1541 cm⁻¹ and 1644 cm⁻¹ (protein amides II and I), and 2930 cm⁻¹ (lipids). In the intergroup analysis, comparing breast cancer, benign breast disease, and healthy controls, it was shown that the biochemical components present in serum and saliva, including lipids, nucleic acids, proteins, and carbohydrates, presented distinct absorbance patterns according to the type of biological fluid analyzed. The 2930 cm⁻¹ peak, related to C–H stretching of lipids in saliva, was able to differentiate the three groups studied. In the second article, the elevated levels of interleukin-1BETA (IL-1BETA) (> 76.03 pg/mL) were associated with worse overall survival (p = 0.018), increasing the risk of death by 8.84 times; and elevated levels of interleukin-10 (IL-10) (> 24.21 pg/mL) were also associated with worse overall survival (p = 0.046), increasing the risk of death by 7.17 times. Red blood cell distribution width (RDW), RDW/platelet ratio (RPR), neutrophil/lymphocyte ratio (N/L), lymphocyte/monocyte ratio (L/M), and interleukin-6 (IL-6) did not show a significant association with prognosis. Conclusions: The results demonstrate that ATR-FTIR spectroscopy is a promising tool for detecting breast cancer from saliva samples, offering advantages such as speed, reproducibility, and non-invasiveness. In parallel, the cytokines IL-1BETA and IL-10 emerge as relevant prognostic biomarkers in advanced disease, reflecting the interaction between systemic inflammation and tumor progression. The integration of these diagnostic and prognostic approaches in the clinical management of breast cancer can contribute to the development of personalized and accessible strategies.