# Dysregulation of Purinergic Signaling Sustains Chronic Inflammation and Oxidative Imbalance in Patients After PitNET Surgical Resection

## TL;DR

This study shows that PitNET patients experience long-term chronic inflammation and oxidative stress after surgery, linked to disrupted purinergic signaling.

## Contribution

The study identifies purinergic signaling dysregulation as a novel factor in post-surgical PitNET patient outcomes.

## Key findings

- PitNET patients had elevated glycemia, ATP levels, and ATP hydrolysis in PBMCs.
- Increased IL-6, IL-10, TNF, and ROS levels were observed, alongside decreased IL-27.
- Patients showed increased non-protein thiols and ascorbic acid despite oxidative imbalance.

## Abstract

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer’s pathophysiology. This study aimed to evaluate the sociodemographic and diagnostic profiles, as well as assess the purinergic signaling, immunological, and redox profiles, of patients after PitNET resection. We collected sociodemographic data and the patients’ diagnostic profiles. We also collected blood samples to analyze glycemia, triglycerides, albumin, and ATP levels. The ectonucleotidase activity was determined in peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their redox and immunological profiles. There was a prevalence of gonadotropic macroadenoma derived from PIT-1 cells. We found that patients included in the PitNET group had increased glycemia, serum ATP levels, and ATP hydrolysis in PBMCs. Analyzing their immunological profiles, we found that patients had increased levels of IL-6, IL-10, and TNF, while the IL-27 level was decreased. Regarding their redox profiles, PitNET patients had increased levels of ROS and protein carbonylation. Unexpectedly, patients also showed increased levels of non-protein thiols (NPSHs), total thiols (PSHs), and ascorbic acid. Thus, the dysregulation of purinergic signaling sustained chronic inflammation and oxidative imbalance in PitNET patients for a long time after surgical resection. These data suggest that patients with PitNETs require long-term accompanying to prevent cancer recurrence prognosis. The biomarkers highlighted in this study may be good tools to help the medical approaches.