Determination of protein markers of inflammasome formation and ferroptosis in thyroid cancer based on gender
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Journal of Cancer
DOI: 10.7150/jca.128886
Authors: Raúl Díaz-Pedrero, Oscar Fraile-Martinez, Cielo García-Montero, Diego Liviu Boaru, Patricia De Castro-Martinez, Diego De Leon-Oliva, Laura López-Gonzalez, Beatriz García-González, Isabel Pérez-González, Majd N. Michael Alhaddadin, Silvestra Barrena-Blázquez, Connie Ferrara-Coppola, Ana María Villar-Carrillo, Laura Gutierrez-Gonzalez, Miguel Pascual-Casero, Félix Mañez, Tomás Ratia Giménez, Inmaculada Lasa-Unzúe, Manuel Díez Alonso, Alberto Gutiérrez-Calvo, Luis G Guijarro, Melchor Álvarez-Mon, Montserrat Chao Crecente, Miguel A Saez, Miguel A Ortega
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,337
OpenAlex ID: W7155408168
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