Efeitos do sistema purinérgico no câncer de tireoide

Abstract

This integrative review examined the role of the purinergic system in thyroid cancer, focusing on the ATP-adenosine axis, the ectonucleotidases CD39 and CD73, and receptors associated with tumor and immune responses. The aim was to understand how these elements relate to tumor progression, the microenvironment, and possible prognostic and therapeutic applications. To do this, direct evidence from thyroid cancer studies was analyzed, together with indirect evidence from other tumor types when relevant, highlighting current gaps in the literature. This was a qualitative, descriptive, and exploratory integrative review based on systematic searches in biomedical databases and original studies assessing expression, activity, experimental modulation, and functional or clinical outcomes related to ATP, adenosine, CD39, CD73, and P1 and P2 receptors. The findings were more consistent for CD73/NT5E, whose expression and activity were associated with lymph node metastasis, extrathyroidal extension, recurrence risk, BRAF-like phenotype, capsular invasion, and migration parameters. Inhibition or silencing of CD73 also reduced proliferation, invasion, migration, and tumor growth. ADORA1 showed increased expression associated with pathological stage and immune infiltration, suggesting a role in tumor response. CD39 also showed increased expression, although with more limited functional support. Even so, studies that assess ATP, adenosine, CD39, CD73, P1/P2 receptors, and immune infiltrate together in the same clinical cohort are still lacking. In conclusion, the purinergic system is involved in tumor progression and microenvironment organization in papillary thyroid carcinoma, especially through CD73/NT5E, but its clinical use still depends on broader and more integrated studies.