Analysis of protein signatures of the extracellular matrix of adrenocortical neoplasms

• Grant number: 23/11931-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Claudimara Ferini Pacicco Lotfi
• Grantee: Henrique Sanchez Ortega
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The adrenal gland is an endocrine gland composed of cortex and medulla. The adrenal cortex presents a structural and functional zonation, whose processes of differentiation, migration, and cell renewal are dependent on interactions betweenligands and intracellular activation pathways. In addition, also to probable interactions between cells and components of the extracellular matrix (ECM). Tumors of the adrenal cortex are classified as adrenocortical adenomas (ACA) and carcinomas(ACC), and other neoplasms such as adrenal hyperplasia (AH). Data from the transcriptome of adrenal tumors show that constitutive activation of some signaling pathways is related to increased expression of several ECM-associated genes. Inthis project, we propose the use of high-throughput proteomics to characterize the ECM of samples of adrenocortical tumors and hyperplasia. We are particularly interested in assessing whether transcriptional activation of ECM genes, such as those induced by certain mutations, are also observed at the protein level. We hypothesize that the composition of the ECM in adrenocortical neoplasms is different, and that this composition may contribute to tumor progression. We hope to identify different ECM proteomic signatures in ACC with prognostic significance, to associate them in the future with different somatic mutations, and thus guide future therapies.