Gasdermin proteins as pyroptosis-based biomarkers in ovarian cancer: Diagnostic and prognostic utility

Current laboratory-based diagnostic approaches for ovarian cancer have important limitations, particularly in early stage detection and clinically meaningful prognostic stratification. Widely used biomarkers, such as CA125 and HE4, can support diagnosis and disease monitoring; however, their sensitivity and specificity remain inadequate across diverse clinical settings, including the evaluation of indeterminate adnexal masses and biologically heterogeneous tumors. Consequently, increasing attention has been directed towards mechanism-based biomarkers that more closely reflect tumor biology and clinically relevant disease states. Among these, gasdermin family proteins, particularly GSDMD, GSDME, and GSDMC, have emerged as promising candidates owing to their central role as executors of pyroptosis and their measurable alterations in tumor tissues and liquid biopsy specimens of patients with cancer. In ovarian tumor tissues, GSDMD and GSDMC are consistently upregulated, whereas GSDME is under expressed or activated in a context-specific manner. Additionally, circulating cleaved fragments were detectable in the serum and plasma, with AUC values supporting this observation. In this review, we discuss the potential of gasdermin-based biomarkers for improving the diagnosis and prognostic assessment of ovarian cancer. We evaluated tissue expression patterns, circulating cleavage-derived signals, epigenetic alterations, and transcriptomic signatures, highlighting their analytical relevance and potential clinical utility. We also examined the laboratory platforms used for their evaluation, including immunohistochemistry, ELISA, quantitative RT-PCR, and multiplex diagnostic approaches, and discussed how the integration of gasdermin-related markers with established biomarkers, such as CA125 and HE, c cand improve diagnostic precision and survival stratification. Finally, we addressed the major requirements for clinical translation, including multicenter analytical validation, commutable reference materials, external quality assessments, and decision-impact studies. The incorporation of gasdermin-based biomarkers into multiparameter diagnostic frameworks could support more accurate disease classification, improved prognostic evaluation, and more individualized management of ovarian cancer.