Evaluation of expression and prognostic value of CXCL9 and CXCL10 genes in pediatric adrenocortical tumors

• Grant number: 21/00932-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2021
• End date: August 31, 2021
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Milena da Silva Ramos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies, AP.TEM

Abstract

Pediatric adrenocortical tumors (ACT), although rare, are neoplasms with an incidence 10-15 times higher in the South and Southeast regions of Brazil. Differently from the adult cases, the differentiation between adenomas and carcinomas based on histopathological criteria or the classification by stage of pediatric ACT are difficult to establish a well-defined prognostic correlation or predict risk of relapse, especially among non-metastatic cases. Currently, in a project of our group funded by FAPESP "Interaction between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on neoplasms in children and adolescents (2014/20341-0)", we have been working with sequencing of pediatric tumors, including ACT, in order to identify possible unpublished biomarkers of prognosis and biological behavior of ACT. The project identified 1215 differentially expressed genes (DEG) among tumors of patients with good (n=9) and poor clinical evolution (metastatic and/or recurrent cases; n=5) in 14 pediatric ACT samples, highlighting the genes CXCL9 and CXCL10, which encode the ligants of the CXCR3 receptor binding chemokines, CXCL9 and CXCL10, respectively. These molecules mediate the recruitment of T lymphocytes and Natural Killer (NK) cells in the tumor microenvironment, both of which were observed underexpressed in the group of patients with metastatic and/or relapsed tumors. Although the high concentrations of these chemokines in tumor tissue are associated with greater lymphocytic infiltrate and better patient survival in several tumors, the role of these genes in ACT is still poorly understood. Thus, the present study aim to validate and evaluate the expression profile of these 2 genes in a larger number of ACT samples from pediatric patients, using the real-time quantitative PCR technique (qRT-PCR), as well as investigating the association between their expression levels with clinicopathological characteristics and patients' clinical outcomes.