{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:16:26Z","timestamp":1793394986263,"version":"4.5.0"},"reference-count":113,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was to identify ferroptosis-associated molecular alterations that are largely shared across subtypes and to evaluate their systemic reflection following localized tissue injury. Tumor and matched normal breast tissues representing major molecular subtypes were analyzed. Global mRNA and miRNA expression profiling was performed using microarrays, followed by validation of selected genes using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Functional enrichment and protein\u2013protein interaction analyses were conducted to characterize associated pathways. In addition, systemic responses were assessed in patients undergoing fibroadenoma cryoablation through longitudinal blood sampling. Six ferroptosis-related genes (SLC7A11, GPX4, FTH1, NQO1, NFE2L2, SQSTM1) demonstrated consistent upregulation across all breast cancer subtypes, with higher expression observed in more aggressive tumors. These genes are functionally linked to antioxidant defense, iron metabolism, and oxidative stress regulation, and their coordinated expression pattern is consistent with activation of NRF2-dependent cytoprotective pathways. Downregulation of selected miRNAs may contribute to this expression profile but likely represents a secondary regulatory mechanism. Survival analysis revealed heterogeneous and subtype-dependent associations, with limited and gene-specific prognostic relevance. Cryoablation induced transient increases in circulating levels of the analyzed proteins, reflecting systemic responses to localized tissue injury. In conclusion, breast cancer is characterized by a largely shared ferroptosis-associated molecular signature across subtypes; however, its clinical impact appears to be variable and context-dependent. Systemic detection of related molecular signals suggests potential utility as indicators of tissue stress responses, although their role as specific biomarkers of ferroptosis requires further validation.<\/jats:p>","DOI":"10.3390\/ijms27083446","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Subtype-Consistent Upregulation of Ferroptosis-Associated Pathways in Breast Cancer with Heterogeneous Prognostic Implications and Systemic Response to Cryoablation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8207-5548","authenticated-orcid":false,"given":"Kacper","family":"Boro\u0144","sequence":"first","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 University in Krak\u00f3w, 30-705 Krak\u00f3w, Poland"},{"name":"Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, 40-055 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"}]},{"given":"Agata","family":"Panfil","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Sirek","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"},{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, 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"}]},{"given":"Agata","family":"Sirek","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, 40-555 Katowice, Poland"},{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-6167","authenticated-orcid":false,"given":"Nikola","family":"Zmarz\u0142y","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michalina","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"},{"name":"Medi-Lab SC, Wr\u00f3bel i Wsp\u00f3lnicy, 58-100 \u015awidnica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"},{"name":"Medi-Lab SC, Wr\u00f3bel i Wsp\u00f3lnicy, 58-100 \u015awidnica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-5829","authenticated-orcid":false,"given":"Dariusz","family":"Boron","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University in Krak\u00f3w, 30-705 Krak\u00f3w, Poland"},{"name":"Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, 40-055 Katowice, Poland"},{"name":"Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, 31-826 Krak\u00f3w, Poland"},{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ossowski","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Ordon","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 in Katowice, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1343-7166","authenticated-orcid":false,"given":"Piotr","family":"Wyrobiec","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Pathology in Zabrze, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Kulej","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Lekston","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-7145","authenticated-orcid":false,"given":"Beniamin Oskar","family":"Grabarek","sequence":"additional","affiliation":[{"name":"Collegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1001\/jama.2023.25881","article-title":"Analysis of Breast Cancer Mortality in the US\u20141975 to 2019","volume":"331","author":"Sun","year":"2024","journal-title":"JAMA"},{"key":"ref_2","first-page":"477","article-title":"Breast Cancer Statistics 2024","volume":"74","author":"Giaquinto","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e34772","DOI":"10.1097\/MD.0000000000034772","article-title":"Differences in Clinical Outcomes between HER2-Negative and HER2-Positive Luminal B Breast Cancer","volume":"102","author":"Kang","year":"2023","journal-title":"Medicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s13058-025-02161-z","article-title":"Evaluation of Short-Course Durvalumab Combined with Dose-Dense EC in the Neoadjuvant Setting for Locally Advanced Luminal B\/HER2(-) or Triple-Negative Breast Cancer","volume":"27","author":"Devaux","year":"2025","journal-title":"Breast Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101968","DOI":"10.1016\/j.suronc.2023.101968","article-title":"Prognostic Factors in Luminal B-like HER2-Negative Breast Cancer Tumors","volume":"49","author":"Soveral","year":"2023","journal-title":"Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2147\/BCTT.S432526","article-title":"Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives","volume":"15","author":"Wang","year":"2023","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Saha, T., and Lukong, K.E. (2022). Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.856974"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"D\u2019Amico, M., and De Amicis, F. (2024). Challenges of Regulated Cell Death: Implications for Therapy Resistance in Cancer. Cells, 13.","DOI":"10.3390\/cells13131083"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s12964-023-01267-1","article-title":"Iron and Copper: Critical Executioners of Ferroptosis, Cuproptosis and Other Forms of Cell Death","volume":"21","author":"Li","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41419-021-04490-1","article-title":"Double-Edge Sword Roles of Iron in Driving Energy Production versus Instigating Ferroptosis","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mortensen, M.S., Ruiz, J., and Watts, J.L. (2023). Polyunsaturated Fatty Acids Drive Lipid Peroxidation during Ferroptosis. Cells, 12.","DOI":"10.3390\/cells12050804"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/ars.2023.0278","article-title":"Dynamic Regulation of Ferroptosis by Lipid Metabolism","volume":"39","author":"Naowarojna","year":"2023","journal-title":"Antioxid. Redox Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1080\/10715762.2023.2244155","article-title":"Defense Systems to Avoid Ferroptosis Caused by Lipid Peroxidation-Mediated Membrane Damage","volume":"57","author":"Fujii","year":"2023","journal-title":"Free Radic. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lu, D., Xia, B., Feng, T., Qi, G., and Ma, Z. (2025). The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications. Biomolecules, 15.","DOI":"10.3390\/biom15050659"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shan, Z., and Liu, F. (2025). Targeting Ferroptosis, Pyroptosis and Necroptosis for Cancer Immunotherapy in Melanoma: Mechanistic Insights and Clinical Perspectives. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1629620"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Glibetic, N., and Weichhaus, M. (2025). Metabolic Regulation of Ferroptosis in Breast Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199686"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, S., Yuan, H., Li, L., Li, Q., Lin, P., and Li, K. (2025). Oxidative Stress and Reprogramming of Lipid Metabolism in Cancers. Antioxidants, 14.","DOI":"10.3390\/antiox14020201"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12943-022-01530-y","article-title":"Ferroptosis in Cancer Therapy: A Novel Approach to Reversing Drug Resistance","volume":"21","author":"Zhang","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/med.21933","article-title":"Ferroptosis-Modulating Small Molecules for Targeting Drug-Resistant Cancer: Challenges and Opportunities in Manipulating Redox Signaling","volume":"43","author":"Koeberle","year":"2023","journal-title":"Med. Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13578-023-01044-0","article-title":"Hinokitiol-Iron Complex Is a Ferroptosis Inducer to Inhibit Triple-Negative Breast Tumor Growth","volume":"13","author":"Zhao","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Riaz, T., Saleem, M.A., Khan, M.U.M., Rashid, M.A.R., and Zubair, M. (2025). Ferroptosis as a Therapeutic Avenue in Triple-Negative Breast Cancer: Mechanistic Insights and Prognostic Potential. Biomedicines, 13.","DOI":"10.3390\/biomedicines13082037"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nie, Z., Chen, M., Gao, Y., Huang, D., Cao, H., Peng, Y., Guo, N., Wang, F., and Zhang, S. (2022). Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.879317"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41420-021-00473-5","article-title":"The Role of Ferroptosis in Breast Cancer Patients: A Comprehensive Analysis","volume":"7","author":"Wu","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, D., Wei, G., Ma, J., Cheng, S., Jia, L., Song, X., Zhang, M., Ju, M., Wang, L., and Zhao, L. (2021). Identification of the Prognostic Value of Ferroptosis-Related Gene Signature in Breast Cancer Patients. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08341-2"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dexheimer, P.J., and Cochella, L. (2020). MicroRNAs: From Mechanism to Organism. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00409"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3390\/stresses4020016","article-title":"Role of microRNA in Oxidative Stress","volume":"4","author":"Saha","year":"2024","journal-title":"Stresses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8812","DOI":"10.1002\/jcp.29724","article-title":"miRNAs, Oxidative Stress, and Cancer: A Comprehensive and Updated Review","volume":"235","author":"Ebrahimi","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"S\u00f8kilde, R., Persson, H., Ehinger, A., Pirona, A.C., Fern\u00f6, M., Hegardt, C., Larsson, C., Loman, N., Malmberg, M., and Ryd\u00e9n, L. (2019). Refinement of Breast Cancer Molecular Classification by miRNA Expression Profiles. BMC Genom., 20.","DOI":"10.1186\/s12864-019-5887-7"},{"key":"ref_29","first-page":"100026","article-title":"Expression of Micrornas in Molecular Genetic Breast Cancer Subtypes","volume":"20","author":"Kolesnikov","year":"2019","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2310856","DOI":"10.1002\/adma.202310856","article-title":"Tissue Ablation: Applications and Perspectives","volume":"36","author":"Keum","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/gs-22-555","article-title":"Clinical Outcomes and Tumor Microenvironment Response to Radiofrequency Ablation Therapy: A Systematic Review and Meta-Analysis","volume":"13","author":"Mueller","year":"2024","journal-title":"Gland. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.rxeng.2021.09.002","article-title":"Cryoablation of Breast Lesions: Our Experience","volume":"64","author":"Villares","year":"2022","journal-title":"Radiolog\u00eda (Engl. Ed.)"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"110632","DOI":"10.1016\/j.clinimag.2025.110632","article-title":"Breast Cryoablation for Management of Benign Fibroadenomas: A Systematic Review of the Literature","volume":"127","author":"Ramgopal","year":"2025","journal-title":"Clin. Imaging"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Song, X., Wang, Z., Tian, Z., Wu, M., Zhou, Y., and Zhang, J. (2023). Identification of Key Ferroptosis-Related Genes in the Peripheral Blood of Patients with Relapsing-Remitting Multiple Sclerosis and Its Diagnostic Value. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076399"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1080\/02656736.2019.1647355","article-title":"Cryoablation: Physical and Molecular Basis with Putative Immunological Consequences","volume":"36","author":"Baust","year":"2019","journal-title":"Int. J. Hyperth."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1152\/physrev.00031.2024","article-title":"Ferroptosis: When Metabolism Meets Cell Death","volume":"105","author":"Zheng","year":"2025","journal-title":"Physiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, Biology and Role in Disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, H., Li, L., Xue, C., Huang, R., Hu, A., An, X., and Shi, Y. (2021). A Novel Ferroptosis-Related Gene Signature Predicts Overall Survival of Breast Cancer Patients. Biology, 10.","DOI":"10.3390\/biology10020151"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17610","DOI":"10.1038\/s41598-021-97102-z","article-title":"A Ferroptosis-Associated Gene Signature for the Prediction of Prognosis and Therapeutic Response in Luminal-Type Breast Carcinoma","volume":"11","author":"Peng","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.5483\/BMBRep.2023-0024","article-title":"Immunogenic Cell Death in Cancer Immunotherapy","volume":"56","author":"Choi","year":"2023","journal-title":"BMB Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/1061186X.2024.2399181","article-title":"Ferroptosis-Targeting Drugs in Breast Cancer","volume":"33","author":"Zhang","year":"2025","journal-title":"J. Drug Target."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ge, A., Xiang, W., Li, Y., Zhao, D., Chen, J., Daga, P., Dai, C.C., Yang, K., Yan, Y., and Hao, M. (2024). Broadening Horizons: The Multifaceted Role of Ferroptosis in Breast Cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1455741"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jyotsana, N., Ta, K.T., and DelGiorno, K.E. (2022). The Role of Cystine\/Glutamate Antiporter SLC7A11\/xCT in the Pathophysiology of Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.858462"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lee, J., and Roh, J.-L. (2022). SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer. Antioxidants, 11.","DOI":"10.3390\/antiox11122444"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1038\/s41467-023-39401-9","article-title":"SLC7A11 Expression Level Dictates Differential Responses to Oxidative Stress in Cancer Cells","volume":"14","author":"Yan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101254","DOI":"10.1016\/j.gendis.2024.101254","article-title":"Regulation of SLC7A11 as an Unconventional Checkpoint in Tumorigenesis through Ferroptosis","volume":"12","author":"Su","year":"2025","journal-title":"Genes Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Li, S., Lu, Z., Sun, R., Guo, S., Gao, F., Cao, B., and Aa, J. (2022). The Role of SLC7A11 in Cancer: Friend or Foe?. Cancers, 14.","DOI":"10.3390\/cancers14133059"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/1471-0528.17327","article-title":"High Co-Expression of SLC7A11 and GPX4 as a Predictor of Platinum Resistance and Poor Prognosis in Patients with Epithelial Ovarian Cancer","volume":"129","author":"Wu","year":"2022","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1080\/15548627.2023.2218764","article-title":"GPX4 in Cell Death, Autophagy, and Disease","volume":"19","author":"Xie","year":"2023","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1800311","DOI":"10.1002\/pmic.201800311","article-title":"GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis","volume":"19","author":"Forcina","year":"2019","journal-title":"Proteomics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1002\/jcp.29232","article-title":"Inhibition of Tumor Propellant Glutathione Peroxidase 4 Induces Ferroptosis in Cancer Cells and Enhances Anticancer Effect of Cisplatin","volume":"235","author":"Zhang","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Song, X., Wang, X., Liu, Z., and Yu, Z. (2020). Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.597434"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.freeradbiomed.2018.10.426","article-title":"Nrf2 Inhibition Reverses Resistance to GPX4 Inhibitor-Induced Ferroptosis in Head and Neck Cancer","volume":"129","author":"Shin","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e70350","DOI":"10.1111\/jcmm.70350","article-title":"Loss of FTH1 Induces Ferritinophagy-Mediated Ferroptosis in Anaemia of Myelodysplastic Syndromes","volume":"29","author":"Yang","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Islam, S., Hoque, N., Nasrin, N., Hossain, M., Rizwan, F., Biswas, K., Asaduzzaman, M., Rahman, S., Hoskin, D.W., and Sultana, S. (2022). Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach. Life, 12.","DOI":"10.3390\/life12070963"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ma, S., Fu, X., Liu, L., Liu, Y., Feng, H., Jiang, H., Liu, X., Liu, R., Liang, Z., and Li, M. (2021). Iron-Dependent Autophagic Cell Death Induced by Radiation in MDA-MB-231 Breast Cancer Cells. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.723801"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"825","DOI":"10.15537\/smj.2021.42.8.20210244","article-title":"Utility of Ferritin and Inflammatory Biomarkers in the Diagnosis of Different Stages of Breast Cancer","volume":"42","author":"George","year":"2021","journal-title":"Saudi Med. J."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chang, V.C., Cotterchio, M., and Khoo, E. (2019). Iron Intake, Body Iron Status, and Risk of Breast Cancer: A Systematic Review and Meta-Analysis. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5642-0"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100977","DOI":"10.1016\/j.drup.2023.100977","article-title":"Fighting Drug-Resistant Lung Cancer by Induction of NAD(P)H:Quinone Oxidoreductase 1 (NQO1)-Mediated Ferroptosis","volume":"70","author":"Yu","year":"2023","journal-title":"Drug Resist. Updates"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/03602532.2019.1632886","article-title":"Drug Metabolizing Enzymes-Associated Chemo Resistance and Strategies to Overcome It","volume":"51","author":"Verma","year":"2019","journal-title":"Drug Metab. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kuang, F., Liu, J., Tang, D., and Kang, R. (2020). Oxidative Damage and Antioxidant Defense in Ferroptosis. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.586578"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101950","DOI":"10.1016\/j.redox.2021.101950","article-title":"The Diverse Functionality of NQO1 and Its Roles in Redox Control","volume":"41","author":"Ross","year":"2021","journal-title":"Redox Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Starcher, C.L., Pay, S.L., Singh, N., Yeh, I.-J., Bhandare, S.B., Su, X., Huang, X., Bey, E.A., Motea, E.A., and Boothman, D.A. (2020). Targeting Base Excision Repair in Cancer: NQO1-Bioactivatable Drugs Improve Tumor Selectivity and Reduce Treatment Toxicity Through Radiosensitization of Human Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01575"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/cas.13537","article-title":"NRF2 Addiction in Cancer Cells","volume":"109","author":"Kitamura","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.32604\/or.2025.065755","article-title":"The Impact of Oxidative Stress and the NRF2-KEAP1-ARE Signaling Pathway on Anticancer Drug Resistance","volume":"33","author":"Verza","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"153","DOI":"10.14348\/molcells.2023.2196","article-title":"Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype","volume":"46","author":"Hallis","year":"2023","journal-title":"Mol. Cells"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103134","DOI":"10.1016\/j.redox.2024.103134","article-title":"Biomarkers of NRF2 Signalling: Current Status and Future Challenges","volume":"72","author":"Morgenstern","year":"2024","journal-title":"Redox Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2174\/1568009617666171002144228","article-title":"Oxidative Stress and Cancer: The Role of Nrf2","volume":"18","author":"Sajadimajd","year":"2018","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1177\/15230864251395963","article-title":"SQSTM1\/P62 Post-Translational Modifications and Reverse Processes Modulate Disease Pathogenesis via KEAP1-NRF2 Signaling and Selective Autophagy","volume":"43","author":"Zhu","year":"2025","journal-title":"Antioxid. Redox Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1080\/15548627.2020.1712108","article-title":"SQSTM1\/P62 Activates NFE2L2\/NRF2 via ULK1-Mediated Autophagic KEAP1 Degradation and Protects Mouse Liver from Lipotoxicity","volume":"16","author":"Lee","year":"2020","journal-title":"Autophagy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s12967-025-06595-z","article-title":"The Dual Role of Autophagy in Cancer Stem Cells: Implications for Tumor Progression and Therapy Resistance","volume":"23","author":"Jia","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s11658-025-00789-5","article-title":"Programmed Cell Death in Triple-Negative Breast Cancer","volume":"30","author":"Liu","year":"2025","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Sun, Y., Xue, Z., Huang, T., Che, X., and Wu, G. (2022). Lipid Metabolism in Ferroptosis and Ferroptosis-Based Cancer Therapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.941618"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41586-023-06983-9","article-title":"7-Dehydrocholesterol Dictates Ferroptosis Sensitivity","volume":"626","author":"Li","year":"2024","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Szulc, A., and Wo\u017aniak, M. (2025). Targeting Ferroptosis as the Achilles\u2019 Heel of Breast Cancer: Mechanisms and Therapeutic Opportunities from a Comprehensive Systematic Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26209902"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cai, X., Zhang, Z., Yang, X., Shen, W., Yuan, L., Ding, X., Yu, Y., and Cai, W. (2025). Unveiling the Impact of Lipid Metabolism on Triple-Negative Breast Cancer Growth and Treatment Options. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1579423"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12943-024-02119-3","article-title":"Altered Metabolism in Cancer: Insights into Energy Pathways and Therapeutic Targets","volume":"23","author":"Tufail","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chembiol.2020.03.013","article-title":"The Chemistry and Biology of Ferroptosis","volume":"27","author":"Stockwell","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"105807","DOI":"10.1016\/j.archoralbio.2023.105807","article-title":"Hsa-miR-26a-5p Improves OSCC Sensitivity to Ferroptosis by Inhibiting SLC7A11","volume":"156","author":"Liang","year":"2023","journal-title":"Arch. Oral Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Fazio, S., Berti, G., Russo, F., Evangelista, M., D\u2019Aurizio, R., Mercatanti, A., Pellegrini, M., and Rizzo, M. (2020). The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells. Cells, 9.","DOI":"10.3390\/cells9020354"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13020-024-01047-0","article-title":"Electroacupuncture Attenuates Ferroptosis by Promoting Nrf2 Nuclear Translocation and Activating Nrf2\/SLC7A11\/GPX4 Pathway in Ischemic Stroke","volume":"20","author":"Yang","year":"2025","journal-title":"Chin. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Tahsin, T., McPhail, D.K., Champion, J.D., Alzahrani, M.A.M., Hilditch, M.L., Faris-Orr, A., Calver, B.L., Cronin, J.G., Mareque-Rivas, J.C., and Sexton, D.W. (2025). Targeting NRF2 and FSP1 to Overcome Ferroptosis Resistance in TSC2-Deficient and Cancer Cells. Cancers, 17.","DOI":"10.20944\/preprints202504.0343.v1"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.clnves.2025.100049","article-title":"Targeting Ferroptosis in Cancer Therapy: Mechanisms, Strategies, and Clinical Applications","volume":"1","author":"Dai","year":"2025","journal-title":"Cell Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41392-024-01969-z","article-title":"Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects","volume":"9","author":"Ru","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12935-025-04019-y","article-title":"Methotrexate-Triggered Ferroptosis Suppresses Oral Cancer Progression by Phosphorylated KEAP1-Mediated NRF2 Degradation to Inhibit SLC7A11\/GPX4 Signaling Pathway","volume":"26","author":"Yu","year":"2026","journal-title":"Cancer Cell Int."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Long, Z., Luo, Y., Yu, M., Wang, X., Zeng, L., and Yang, K. (2024). Targeting Ferroptosis: A New Therapeutic Opportunity for Kidney Diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1435139"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Din, M.A.U., Lin, Y., Wang, N., Wang, B., and Mao, F. (2024). Ferroptosis and the Ubiquitin-Proteasome System: Exploring Treatment Targets in Cancer. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1383203"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Dai, S.-M., Li, F.-J., Long, H.-Z., Zhou, Z.-W., Luo, H.-Y., Xu, S.-G., and Gao, L.-C. (2022). Relationship between miRNA and Ferroptosis in Tumors. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.977062"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1007\/s12672-025-03507-x","article-title":"Ferroptosis and Non-Coding RNAs in Breast Cancer: Insights into CAF and TAM Interactions","volume":"16","author":"Saadh","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1186\/s12967-023-04370-6","article-title":"Ferroptosis in Tumors and Its Relationship to Other Programmed Cell Death: Role of Non-Coding RNAs","volume":"21","author":"Zhang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mahmoudi-Lamouki, R., Kadkhoda, S., Hussen, B.M., and Ghafouri-Fard, S. (2023). Emerging Role of miRNAs in the Regulation of Ferroptosis. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1115996"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s10238-025-01766-0","article-title":"MicroRNAs at the Crossroads of Exercise and Ferroptosis: A Regulatory Bridge","volume":"25","author":"Lin","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.rxeng.2022.12.011","article-title":"Ultrasound-Guided Cryoablation: Our Experience in Percutaneous Treatment as an Alternative to Surgery for Fibroadenomas of the Breast Lesions","volume":"66","year":"2024","journal-title":"Radiolog\u00eda (Engl. Ed.)"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e202300379","DOI":"10.1002\/ange.202300379","article-title":"Ferroptosis Detection: From Approaches to Applications","volume":"135","author":"Zeng","year":"2023","journal-title":"Angew. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1080\/1061186X.2021.1971237","article-title":"Targetting Ferroptosis for Blood Cell-Related Diseases","volume":"30","author":"Chen","year":"2022","journal-title":"J. Drug Target."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1080\/15548627.2024.2319901","article-title":"International Consensus Guidelines for the Definition, Detection, and Interpretation of Autophagy-Dependent Ferroptosis","volume":"20","author":"Chen","year":"2024","journal-title":"Autophagy"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41419-023-05716-0","article-title":"The Interaction between Ferroptosis and Inflammatory Signaling Pathways","volume":"14","author":"Chen","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhang, H., Chen, N., Ding, C., Zhang, H., Liu, D., and Liu, S. (2024). Ferroptosis and EMT Resistance in Cancer: A Comprehensive Review of the Interplay. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1344290"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1021\/acs.jmedchem.3c01749","article-title":"Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer","volume":"67","author":"Shi","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Panfil, A., Sirek, T., Sirek, A., Zmarz\u0142y, N., Wr\u00f3bel, M., Wr\u00f3bel, Z., Boro\u0144, K., Boro\u0144, D., Ossowski, P., and Stefaniak, M. (2026). Integrated Transcriptomic, Protein, and MicroRNA Profiling Reveals a Conserved Pyroptosis-Related Molecular Signature across Breast Cancer Subtypes. Front. Mol. Biosci., 13.","DOI":"10.3389\/fmolb.2026.1759944"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Sirek, T., Sirek, A., Borawski, P., Zmarz\u0142y, N., Su\u0142kowska, J., Kr\u00f3l-Jatr\u0119ga, K., Op\u0142awski, M., Boro\u0144, D., Chalcarz, M., and Ossowski, P. (2024). miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810088"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sirek, T., Sirek, A., Op\u0142awski, M., Boro\u0144, D., Chalcarz, M., Ossowski, P., Dziobek, K., Zmarz\u0142y, N., Strojny, D., and Grabarek, B.O. (2024). Expression Profile of Messenger and Micro RNAs Related to the Histaminergic System in Patients with Five Subtypes of Breast Cancer. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1407538"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Sirek, T., Sirek, A., Borawski, P., Rygu\u0142a, I., Kr\u00f3l-Jatr\u0119ga, K., Op\u0142awski, M., Boro\u0144, D., Chalcarz, M., Ossowski, P., and Dziobek, K. (2024). Expression Profiles of Dopamine-Related Genes and miRNAs Regulating Their Expression in Breast Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126546"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1470-2045(17)30438-2","article-title":"The TNM Classification of Malignant Tumours\u2014Towards Common Understanding and Reasonable Expectations","volume":"18","author":"Brierley","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting Effective microRNA Target Sites in Mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"eLife"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"miRDB: An Online Database for Prediction of Functional microRNA Targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13059-019-1629-z","article-title":"Prediction of Functional microRNA Targets by Integrative Modeling of microRNA Binding and Target Expression Data","volume":"20","author":"Liu","year":"2019","journal-title":"Genome Biol."},{"key":"ref_109","first-page":"100625","article-title":"Integrated Analysis of Public Datasets for the Discovery and Validation of Survival-Associated Genes in Solid Tumors","volume":"5","year":"2024","journal-title":"Innovation"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/bph.16257","article-title":"Transcriptome-Level Discovery of Survival-Associated Biomarkers and Therapy Targets in Non-Small-Cell Lung Cancer","volume":"181","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein\u2013Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_112","unstructured":"(2022, April 19). Kalkulator Doboru Pr\u00f3by. Available online: https:\/\/www.naukowiec.org\/dobor.html."},{"key":"ref_113","unstructured":"Krajowy Rejestr Nowotwor\u00f3w (2024, February 01). Nowotw\u00f3r Piersi-2019. Available online: https:\/\/onkologia.org.pl\/sites\/default\/files\/Pier%C5%9B.pdf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:57:51Z","timestamp":1776070671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":113,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083446"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083446","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}