Dados do Resumo

Título

Metabolomic profile of placentas from patients who had breast cancer during pregnancy and underwent chemotherapy treatment.

Introdução

Cancer during pregnancy is rare, with an incidence of 1:1000 pregnancies, and breast cancer (BC) is the most common. It is known that the combination of breast cancer and chemotherapy treatment during pregnancy is a stress factor for the placenta, which can consequently lead to adverse effects on the fetus, such as intrauterine growth restriction and preterm birth. Despite its high clinical relevance, little is known about the alterations that occur in the placenta, especially at the omics level. Among the omics, metabolomics is the tool closest to the phenotype and provides clinical insights.

Objetivo

In this context, the objective of this study is to investigate the metabolomic profile of placentas from patients who had breast cancer during pregnancy and underwent chemotherapy treatment.

Métodos

For this purpose, 16 placentas from patients were collected and stored in the Center for Integral Attention to Women’s Health biobank/UNICAMP (CONEP registration B-056), with 8 placentas from patients with breast cancer treated with chemotherapy (Case group) and 8 placentas from patients with habitual risk (Control group) (CAAE: 65070122.0.0000.5404). The analyses are being conducted in the chorionic villi region, and so far, 3 samples (Case group) have been extracted through homogenization with methanol and chloroform. The polar metabolites have been collected for analysis using nuclear magnetic resonance (NMR) at the National Synchrotron Light Laboratory/National Center for Research in Energy and Materials. The spectra obtained by NMR were identified and quantified using Chenomx software, with subsequent normalization of metabolite concentrations based on the sample weights. Finally, after processing the remaining samples from the Case and Control groups, the data will be compared using the T-test (Prisma Software) and related to biological function.

Resultados

In the three spectra analyzed, 54 metabolites were identified. The metabolites with the highest concentrations were lactate, taurine, glutamate, choline, and glucose, while AMP, succinate, fumarate, pantothenate, and NAD+ had lower concentrations. High lactate concentration suggests that the glycolytic pathway is active in this tissue, possibly due to the tumor's high energy consumption. High taurine concentrations may indicate protection against oxidative stress, and glutamate is associated with cell proliferation. The high concentration of choline indicates an increased demand for phospholipids, and elevated glucose reflects a greater energy need. Low concentrations of AMP, succinate, and fumarate suggest dysfunctions in the regulation of energy homeostasis and mitochondrial function. Low pantothenate levels may impair fatty acid synthesis, and low NAD+ is associated with oxidative stress. To date, three samples have been analyzed, with plans to include additional samples (case and control) before the conference.

Conclusões

Metabolic changes may indicate potential adaptations of the placental environment in response to stress associated with breast cancer and chemotherapy during pregnancy. Continuing the analyses with samples from both the Case and Control groups will be crucial for understanding the consequences of breast cancer during pregnancy associated with chemotherapy treatment on maternal-fetal health.

Financiador do resumo

FAPESP – São Paulo Research Foundation (process numbers: 2023/09916-0; 2021/08931-0).

Palavras Chave

Breast cancer; Placenta; and Metabolomics