Determination of protein markers of inflammasome formation and ferroptosis in thyroid cancer based on gender.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, with a globally increasing incidence. The disease exhibits significant sex-related clinical and biological differences: while incidence is approximately three times higher in women, men face a greater risk of lymph node metastasis, recurrence, and mortality. This gender disparity may be associated with hormonal factors, particularly estrogens, which are known to modulate cellular proliferation, invasion, migration, and adhesion in thyroid tumor cells. However, the molecular pathways underlying these effects remain poorly understood. In this context, the hallmarks of cancer proposed by Hanahan-such as sustained proliferative signaling, evasion of cell death, and reprogramming of the tumor microenvironment-provide a valuable framework to investigate sex-based disparities. This study assessed, via immunohistochemistry, the expression of molecular markers related to ferroptosis (GPX4, ALOX5, ACSL4, TFRC), the NLRP3 inflammasome and its components (NLRP3, ASC, caspase-1, caspase-5, caspase-8, IL-1β, and IL-18), proliferation (IRS-4), and tumor suppression (KLOTHO) in PTC samples from 25 men and 25 women. Our results demonstrated increased expression of ferroptosis-related markers, components of the NLRP3 inflammasome, and IRS-4 in female-derived samples, whereas male samples exhibited higher KLOTHO expression levels. These findings support the hypothesis of a molecular basis for sexual dimorphism in PTC and highlight the need for further research with larger cohorts and mechanistic approaches to elucidate these pathways and their therapeutic potential.