Impact of nitrosative stress and endothelial damage on angioinvasive papillary thyroid cancer

Papillary thyroid cancer (PTC) typically has a favorable prognosis. However, in some cases, the presence of angioinvasion can result in local invasion, recurrence, and distant metastasis, leading to poorer outcomes. Identifying disrupted pathways associated with angioinvasion could lead to the discovery of novel angioinvasive markers in PTC, which, in turn, may suggest more aggressive clinical management strategies, as radioiodine therapy (RAI). This study aims to identify potential markers associated with angioinvasive PTC, with a particular focus on nitrosative stress and endothelial damage. For the purpose of this study, 45 patients with angioinvasive PTC (study group) and 45 patients without angioinvasion and characterized by a very low risk of cancer progression (reference group) were enrolled. We assessed the levels of total antioxidant capacity (TAC), 3-nitrotyrosine (3-NT), placental growth factor (PLGF), integrin subunit alpha V (ITGAV), and integrin subunit alpha V beta 3 (ITGαVβ3) as potential markers for angioinvasion. Our results revealed significant alterations in the concentration patterns of these markers, suggesting their potential utility as screening tools for angioinvasion and as prognostic indicators in PTC patients. Specifically, elevated levels of 3-NT, PLGF, ITGAV, and ITGαVβ3 were observed, while TAC levels were decreased in the study group compared to the reference group (all, p < 0.05). Logistic regression analysis confirmed a significant association of TAC, 3-NT, and PLGF with the occurrence of angioinvasion. PLGF demonstrated an area under the curve (AUC) of 0.82, indicating its clinical significance. However, to enhance screening utility for clinical management, a panel consisting of 3-NT, TAC, and PLGF assessments was created, demonstrating the highest potential utility as an angioinvasion screening tool (3-NT + TAC + PLGF AUC = 0.95).