ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Integrated Transcriptomic, Protein, and MicroRNA Profiling Reveals a Conserved Pyroptosis-Related Molecular Signature Across Breast Cancer Subtypes
Agata Panfil 1
Tomasz Sirek 1
Agata Sirek 1
Nikola Zmarzły 1
Michalina Wróbel 1
Zbigniew Wróbel 1
Kacper Boroń 1
Dariusz Boron 1
Piotr Ossowski 1
Martyna Stefaniak 1
Paweł Ordon 1
Grzegorz Wyrobiec 2
Piotr Wyrobiec 2
Beniamin Oskar Grabarek 1
1. Akademia WSB, Dabrowa Gornicza, Poland
2. Slaski Uniwersytet Medyczny w Katowicach, Katowice, Poland
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Abstract
Background: Pyroptosis, an inflammatory form of programmed cell death, has been implicated in tumor progression, yet its molecular contribution across breast cancer subtypes remains poorly defined. Methods: To characterize pyroptosis-related alterations, we analyzed tumor and matched control tissues from five molecular subtypes of breast cancer using genome-wide messenger RNA and microRNA microarrays, quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and protein–protein interaction analysis. We identified predicted microRNA–messenger RNA regulatory relationships and constructed a pyroptosis index and inflammasome activation score. To contextualize these findings, temporal expression changes were evaluated in a cryoablation model of benign fibroadenoma. Results: Nine genes associated with inflammatory and apoptotic signaling—CXCL8, BCL2, BAX, CASP1, CASP9, TP53, CDKN1A, CDKN1B, and MMP9—consistently distinguished cancerous from control tissue across all subtypes at both messenger RNA and protein levels. Aggressive subtypes, particularly human epidermal growth factor receptor 2–enriched and triple-negative tumors, exhibited pronounced activation of inflammasome-related pathways, elevated pyroptosis index and inflammasome activation score values, and coordinated suppression of cell-cycle inhibitors. Predicted microRNA regulators, including microRNA 140-3p, microRNA 124-3p, microRNA 300, microRNA 30a-3p, microRNA 30d-3p, and microRNA 608, showed patterns consistent with loss of post-transcriptional restraint in high-grade tumors. In fibroadenoma, pyroptosis-associated expression changes were rapid and transient, whereas malignant tissue displayed a consistent, subtype-dependent elevation of pyroptosis-related markers at the time of resection. Conclusion: This integrative analysis identifies a conserved pyroptosis-related molecular signature that deepens understanding of inflammatory programmed cell death in breast cancer and highlights interconnected pathways with diagnostic, prognostic, and therapeutic relevance.
Summary
Keywords
breast cancer, Cell Death, micro RNA, molecular marker, pyroptosis
Received
03 December 2025
Accepted
30 January 2026
Copyright
© 2026 Panfil, Sirek, Sirek, Zmarzły, Wróbel, Wróbel, Boroń, Boron, Ossowski, Stefaniak, Ordon, Wyrobiec, Wyrobiec and Grabarek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Agata Panfil
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