Alimentação, metilação e expressão do microRNA-375, e prognóstico em carcinoma espinocelular de cabeça e pescoço

Abstract

The objective of this study was to identify whether the methylation pattern of MIR375 and the expression of miR-375 are associated with diet and prognostics factors in patients with head and neck squamous cell carcinoma (HNSCC). This study was conducted in two stages. The first stage was a cross-sectional study that included individuals of both sexes, aged between 20 and 80 years, who were newly diagnosed and in the pre-treatment phase of HNSCC. Sociodemographic, anthropometric, lifestyle, and clinical data were collected, including tumor staging, cellular differentiation, and biochemical tests. Dietary intake was assessed using a food frequency questionnaire. Dietary patterns were determined through principal component analysis. Additionally, dietary intake was evaluated according to the degree of food processing using the NOVA classification. The second stage consisted of a bioinformatics study based on data from The Cancer Genome Atlas (TCGA). This stage aimed to assess the prognostic value of the methylation pattern in the gene regions of MIR375 and subsequently select promoter regions for further study. The association between dietary patterns and clinical data was evaluated using multinomial logistic regression. The association between diet, as classified by NOVA, and inflammatory markers was assessed using multiple linear regression. The prognostic value of the molecular results from the bioinformatics analysis was evaluated using Kaplan-Meier survival curves for overall and disease-free survival and Cox regression. Regarding the results, three dietary patterns were identified: "healthy," "processed," and "mixed." The "processed" dietary pattern was associated with stage III (OR: 2.47; 95% CI: 1.43–4.26; p = 0.001) and stage IV (OR: 1.78; 95% CI: 1.12–2.84; p = 0.015) of HNSCC. No association was found between dietary patterns and cellular differentiation (p > 0.05). Regarding the NOVA classification, the processed food group was positively associated with the systemic immune-inflammation index (β: 1.95 x 10³; p = 0.045) and the neutrophil-to-lymphocyte ratio (β: 5.93 x 10³; p = 0.003). In relation to the bioinformatics study, hypermethylation of the N shore region of MIR375 was an unfavorable predictor for overall survival (RR: 1.63; 95% CI: 1.11–2.40; p = 0.014) and disease-free survival (RR: 1.80; 95% CI: 1.13–2.88; p = 0.013). Thus, greater adherence to a dietary pattern composed of processed foods was associated with more advanced stages of HNSCC and inflammatory markers. DNA methylation in regions that may influence miR-375 expression can be considered a predictor of survival in HNSCC, particularly in the N Shore region. This study presents relevant preliminary results on the relationship between diet, epigenetic mechanisms, and prognosis in HNSCC, guiding future studies that may complement the main investigation and deepen the conclusions found.