{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:06:09Z","timestamp":1788944769864,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Apoptosis maintains tissue homeostasis, and its dysregulation is closely associated with breast cancer progression and therapeutic resistance. We performed an integrative analysis of apoptosis-related signaling in breast cancer tissues across five molecular subtypes and compared these patterns with systemic apoptotic responses following cryoablation of benign fibroadenomas. Gene expression profiling was conducted using mRNA microarrays and validated by qRT-PCR and ELISA. Apoptosis pathway activity was assessed with the MSigDB HALLMARK_APOPTOSIS gene set, including intrinsic and extrinsic pathway scoring and an apoptotic balance index (ABI). MicroRNA profiling combined with in silico analyses identified potential miRNA\u2013mRNA interactions. A progressive shift toward reduced pro-apoptotic and enhanced stress-adaptive signaling was observed with increasing tumor aggressiveness, most pronounced in triple-negative and non-luminal HER2-positive cancers. This pattern included reduced intrinsic pathway activity, decreased ABI, downregulation of pro-apoptotic genes (BIK, BMF, TXNIP), and upregulation of stress-associated or cytoprotective genes (HSPB1, PPT1). Several expression patterns were accompanied by overexpression of miRNAs (miR-582-5p, miR-421, miR-106b-5p, miR-20a-5p, miR-20b-5p, miR-93-5p) predicted to target apoptosis-related genes. In contrast, fibroadenoma cryoablation was associated with transient systemic modulation of apoptosis-related genes and proteins followed by gradual normalization. These findings highlight differences between apoptosis-related dysregulation in malignant tissue and regulated systemic responses following benign tissue injury, supporting pathway-level interpretation and identifying candidate molecular networks warranting further mechanistic and translational investigation.<\/jats:p>","DOI":"10.3390\/ijms27125174","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:43:46Z","timestamp":1780897426000},"page":"5174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Apoptotic Signaling Across Breast Cancer Subtypes and Cryoablation-Induced Tissue Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Agata","family":"Panfil","sequence":"first","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Kacper","family":"Boro\u0144","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"},{"name":"Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Krak\u00f3w, Poland"},{"name":"Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, 40-662 Katowice, Poland"},{"name":"Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, 31-826 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Tomasz","family":"Sirek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"},{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"},{"name":"Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Bia\u0142a, 43-316 Bielsko-Biala, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Agata","family":"Sirek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, 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Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ossowski","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-8379","authenticated-orcid":false,"given":"Martyna","family":"Stefaniak","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Pawe\u0142","family":"Ordon","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Grzegorz","family":"Wyrobiec","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Wojciech","family":"Kulej","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 D\u0105browa G\u00f3rnicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8395-279X","authenticated-orcid":false,"given":"Marcin","family":"Op\u0142awski","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski 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