Characterization of CTSL expression in wild-type IDH glioblastomas and analysis of its role as a biomarker of response to therapy.

• Grant number: 23/08628-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Lucas Tadeu Bidinotto
• Grantee: Natália Portruneli
• Host Institution: Faculdade de Ciências da Saúde de Barretos Dr Paulo Prata (FACISB). Barretos , SP, Brazil

Abstract

Despite advances in molecular discoveries of Glioblastomas (GBM) IDH wild type, treatment success is reserved, with the use of the same standard therapy for all patients. Our research group described a signature of 12 genes associated with patients diagnosed with GBM with low survival, and CTSL proved to be important in several in silico analyses. Other articles show the high expression of this gene associated with the polarization of macrophages towards M2 and associated with resistance to treatment and/or increased migration and neoplastic invasion. Therefore, this project aims to characterize the expression of CTSL and propose treatment strategies for patients with high expression of this gene. Characterization of CTSL expression will be performed in a cohort of 80 patients diagnosed with GBM IDH wild type and in cell lines. Then, this gene will be silenced by CRISPR and functional assays of proliferation, apoptosis, migration and invasion will be performed. Cells silenced for CTSL will also be placedin co-culture with M1 and M2 macrophages for analysis of macrophage function. Then, the polarization capacity of macrophages will be analyzed by treating undifferentiated macrophages with medium conditioned by tumor cells silenced for CTSL or not. Finally, in silico analysis of potential compounds for the treatment of patients with high expression of CTSL will be performed, and these compounds will be tested in vitro in cells silenced or not for this gene through MTS analysis.