{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:39:51Z","timestamp":1790361591985,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health\u2014HUB LIFE SCIENCE\u2014Advanced Diagnostic\u2013Italian network of excellence for advanced diagnosis","award":["INNOVA"],"award-info":[{"award-number":["INNOVA"]}]},{"name":"Ministry of Health\u2014HUB LIFE SCIENCE\u2014Advanced Diagnostic\u2013Italian network of excellence for advanced diagnosis","award":["PNC-E3-2022-23683266"],"award-info":[{"award-number":["PNC-E3-2022-23683266"]}]},{"name":"European Union NextGenerationEU","award":["CUP: E83C22004670001"],"award-info":[{"award-number":["CUP: E83C22004670001"]}]},{"name":"Associazione Italiana per la Ricerca contro il Cancro","award":["IG 2022 ID 27366"],"award-info":[{"award-number":["IG 2022 ID 27366"]}]},{"name":"Associazione Italiana per la Ricerca contro il Cancro","award":["IG#31044"],"award-info":[{"award-number":["IG#31044"]}]},{"name":"RC\/Fondazione Luigi Maria Monti"},{"name":"\u201cMinistero dell\u2019Universit\u00e0 e della Ricerca\u201d PRIN2022","award":["2022TXHFSA"],"award-info":[{"award-number":["2022TXHFSA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer is the leading cause of cancer-related death in women, and despite advances in preventive screening as well as in molecular classification, many patients still do not benefit from existing therapies, highlighting the importance of identifying new molecular determinants of treatment resistance. The Paired-box (PAX) family of developmental transcription factors are central regulators of tissue morphogenesis and lineage specification, yet their reactivation in tumors and contribution to breast cancer progression remain only partially defined. Here, a multi-level analysis integrating RNA sequencing and protein profiling in twenty-one primary breast carcinomas shows that distinct PAX members are directly correlated to distinct fundamental cancer hallmarks, including proliferation, cell death, epithelial\u2013mesenchymal transition, immune evasion, and genomic instability. Specifically, PAX1 and PAX9 correlates with both cell death and proliferative markers, indicating dual roles in the regulation of cell fate. PAX1 and PAX9 correlate with both proliferative and apoptotic markers, indicating dual roles in cell fate regulation. PAX3, PAX5, and PAX8 are mainly associated with immune checkpoint expression, including PD-L1 and TIGIT, while PAX6 is linked to microsatellite instability and tumor mutational burden, implicating it in genomic dysregulation. Therefore, PAX-based molecular signatures identify that accurately predict lymph node metastasis at transcriptomic (PAX2\u2013PAX7) levels. These findings establish PAX transcription factors as key modulators of breast cancer biology and support their potential as clinically relevant biomarkers for prognostic refinement and therapeutic stratification.<\/jats:p>","DOI":"10.3390\/ijms27041988","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:44:27Z","timestamp":1771501467000},"page":"1988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Paired-Box (PAX) Gene Signatures as a Biomarker of Breast Cancer Progression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-1309","authenticated-orcid":false,"given":"Manuel","family":"Scimeca","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Scioli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Funke","sequence":"additional","affiliation":[{"name":"Indivumed GmbH, Falkenried, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Woodsmith","sequence":"additional","affiliation":[{"name":"Indivumed GmbH, Falkenried, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2619-9153","authenticated-orcid":false,"given":"Francesca","family":"Servadei","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-3527","authenticated-orcid":false,"given":"Erica","family":"Giacobbi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8673-2775","authenticated-orcid":false,"given":"Christian","family":"Seghetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oreste Claudio","family":"Buonomo","sequence":"additional","affiliation":[{"name":"Breast Unit Policlinico Tor Vergata, Department of Surgical Science, Tor Vergata University, Viale Oxford 81, 00133 Rome, Italy"},{"name":"Department of Health Science, University of Basilicata, Via Nazario Sauro, 85, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Candi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Biochemistry Laboratory, Istituto Dermopatico Immacolata (IDI-IRCCS), Via Monti di Creta n.106, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-2604","authenticated-orcid":false,"given":"Michele","family":"Treglia","sequence":"additional","affiliation":[{"name":"Laif (Laboratorio di Antropologia e Invecchiamento Forense), Sezione di Medicina Legale, Sicurezza Sociale e Tossicologia Forense, University of Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Biomedicine and Prevention, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Tonino","family":"Marsella","sequence":"additional","affiliation":[{"name":"Laif (Laboratorio di Antropologia e Invecchiamento Forense), Sezione di Medicina Legale, Sicurezza Sociale e Tossicologia Forense, University of Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Biomedicine and Prevention, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-5972","authenticated-orcid":false,"given":"Gerry","family":"Melino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-5676","authenticated-orcid":false,"given":"Alessandro","family":"Mauriello","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Bonfiglio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, TOR, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","unstructured":"(2026, January 05). 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