Scholarship 24/15577-6 - Integração, Placenta - BV FAPESP
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Omics integration of placental chorionic villi in pregnant women with breast cancer undergoing chemotherapy treatment

Grant number: 24/15577-6
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Start date until: January 27, 2025
End date until: July 26, 2025
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Laís Rosa Viana
Grantee:Rafaella Trevisan Scandiuzzi
Supervisor: Olivier e Pardo
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Institution abroad: Imperial College London, England  
Associated to the scholarship:23/09681-2 - Cancer and pregnancy: Assessment of placental oxidative and glycolytic metabolism in patients with breast cancer submitted to chemotherapy., BP.MS

Abstract

Cancer is a significant global public health issue due to its high mortality rates, with approximately 20 million new cases in 2022. Breast cancer is the most common among women, and there has been an increase in diagnoses among younger women, including during pregnancy. Breast cancer during pregnancy associated with chemotherapy can lead to alterations in the placenta leading to intrauterine growth restriction and preterm birth. Despite the key role that placenta has in the context of pregnancy, little is known about molecular mechanisms that are altered in the context of breast cancer during pregnancy (PrBC) and chemotherapy treatment. To have a holistic view and better understand the molecular pathways that could be involved on the placenta alterations related to PrBC, the integration of omics analysis combined with clinical data is essential. Therefore, the aim of this project is to perform integrated analyses of proteomics, and metabolomics on placentas from PrBC patients undergoing chemotherapy and to compare these results with the integrated omic profiles of placentas from low-risk pregnancies (Control group). To achieve this objective, the Young Researcher project (2021/08931-0) has partnerships with CAISM and LNBIO (CNPEM). At CAISM, the placentas from PrBC and control patients were collected and stored, while at LNBIO, metabolomic analyses are being conducted using the Varian Inova NMR spectrometer 600Hz (Agilent Technologies Inc., Santa Clara, CA, USA). The proteomic analysis is being performed using a two-dimensional nano UPLC (2D-RP/RP) in an Acquity UPLC M-Class System (Waters Corporation, MA, USA), which is connected in line to a Synapt G2-Si mass spectrometer (Waters Corporation). The mass spectrometer executes Data-Independent Acquisitions, specifically employing Ultra-definition Data-independent Mass Spectrometry (UDMSE). The next steps of cleaning, formatting, integration (using R), and biological enrichment of these data is the BEPE project, which will be carried out in London, at Imperial College, in collaboration with Dr. Oliver Pardo's group, a leading team in omics integration. Therefore, the cleaning and formatting of these data will be conducted. A list of differentially expressed proteins (DEPs) and metabolites (DEMs) between conditions will be generated through statistical analysis using ANOVA with correction for multiple comparisons (false discovery rate method). DEPs will undergo static multivariate functional interaction network analysis using ReactomeFIViz (Cytoscape). Additionally, pathway enrichment will be performed for subsequent integration with DEMs. The correspondence between DEMs and DEPs will be visualized by overlapping them on the HumanCyc database's metabolic map. Additionally, potential changes in transcription factor activity that may explain the DEPs will be inferred using iRegulon. Finally, correlation analysis between DEPs/DEMs and the clinical data associated with the datasets will be performed.

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