Evaluation of the clinical and functional significance of the PRKAB2 gene in pediatric adrenocortical tumor

• Grant number: 21/10702-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2022
• End date: February 28, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Alcides Euzebio Tavares Xavier
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Pediatric adrenocortical tumor (ACT) is a rare neoplasm with poor prognosis in advanced cases. These tumors have a high heterogeneity, and the anatomopathological parameters used are considered inaccurate and so far, it is not possible to establish a well-defined prognostic correlation, which reflects difficulties in determining the progression of the disease and target-treatment. Complete surgical resection is the only therapeutic option with a potential for cure. Due to the scarcity of information about the biology of ACTs, especially in pediatric cases, it becomes a challenge to understand the molecular mechanisms of initiation/development and progression of these tumors. In this context, we highlight the AMP-activated protein kinases (AMPK), which has the PRKAB2 gene as a producer of one of the subunits of the AMPK complex and which exert crucial activities for the maintenance of embryonic development, and are strongly associated with the main hallmarks of cancer, such as: proliferation, migration and cell death. Previous results from our research group identified the PRKAB2 gene as a hypoexpressed hub gene in ACT through in silico analyzes in public databases and by RNA-Sequencing (RNA-Seq) data in an in-house cohort. Surprisingly, PRKAB2 underexpression was associated with worse disease prognosis. Based on these findings, it is crucial to continue this pioneering project and to explore the role of PRKAB2 in pediatric ACT, in order to characterize and explore its biological molecular functions related to the mechanisms of invasiveness, chemoresistance, proliferation and cell death. Furthermore, it would be also important to evaluate the putative crosstalks of this gene with embryonic developmental pathways in order to provide new insights for prognosis, diagnosis and clinical direction.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

XAVIER, Alcides Euzebio Tavares. PRKAB2 as a prognostic biomarker and Rottlerin as a potential chemotherapeutic for pediatric adrenocortical tumor. 2023. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.