Análise da expressão gênica e proteica do PD-L1 e do CD73 como biomarcadores de prognóstico em pacientes com glioblastoma

Abstract

Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous tissue, presenting a critical clinical course and an unfavorable prognosis. Its biological behavior is associated with the induction of an immunosuppressive state through the modulation of components of the tumor microenvironment. Immunosuppression enables these tumors to evade immune surveillance and become resistant to immunotherapies. The Programmed Cell Death pathway, represented by the PD-1 and PD-L1 ligands, as well as the adenosinergic axis, mediated by the activity of the CD73 enzyme, play important roles in the immunomodulatory nature of GBM. In this study, we evaluated the protein production and gene expression of CD73 and PD-L1, as well as their prognostic predictive potential in tumor samples from patients with GBM. This is a non-interventional cross-sectional study. The study group consisted of 42 participants diagnosed with grade II, III, and IV gliomas who were eligible for surgery. They were divided into two groups: Low-Grade Gliomas (LGG) (n=21) and GBM (n=21). The samples were subjected to immunohistochemistry and RT-qPCR analyses, and complementary data were obtained from public databases of international health agencies. Immunohistochemistry analysis identified higher protein production through PD-L1 and CD73 immunoreactivity in the GBM group compared to the LGG group (p=0.014 and p=0.021, respectively). Gene expression analysis showed no statistically significant differences between the groups for either PD-L1 (p=0.616) or CD73 (p=0.070). However, a strong and statistically significant positive correlation was observed between PD-L1 and CD73 in GBM (r=0.714; p=0.003), while in LGG the correlation was not significant (p=0.255). These findings suggest that in GBM, the immunosuppressive pathways mediated by PD-L1 and CD73 may act interdependently, indicating a more immunosuppressive tumor microenvironment. Overall survival analysis showed no statistically significant difference for PD-L1 (p=0.214) or CD73 (p=0.370). However, a significant association was found between higher PD-L1 gene expression and lower progression-free survival rates (p=0.002). Our findings indicate that the protein production and gene expression of these immunosuppressive markers are present in human GBM tumor tissue and may directly impact clinical outcomes in this population.