{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:32:25Z","timestamp":1790573545770,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III-Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la Investigaci\u00f3n","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"Instituto de Salud Carlos III-Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la Investigaci\u00f3n","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"Instituto de Salud Carlos III-Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la Investigaci\u00f3n","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]},{"name":"European Union","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"European Union","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"European Union","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]},{"name":"Janssen-Pharmaceuticals","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"Janssen-Pharmaceuticals","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"Janssen-Pharmaceuticals","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]},{"name":"Contracte Cl\u00ednic Recerca \u201cEmili Letang i Josep Font\u201d","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"Contracte Cl\u00ednic Recerca \u201cEmili Letang i Josep Font\u201d","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"Contracte Cl\u00ednic Recerca \u201cEmili Letang i Josep Font\u201d","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]},{"name":"\u2018\u2018Ayudas SEOM de Intensificaci\u00f3n para Investigadores J\u00f3venes\u2019\u2019","award":["PI18\/00714"],"award-info":[{"award-number":["PI18\/00714"]}]},{"name":"\u2018\u2018Ayudas SEOM de Intensificaci\u00f3n para Investigadores J\u00f3venes\u2019\u2019","award":["PI24\/00631"],"award-info":[{"award-number":["PI24\/00631"]}]},{"name":"\u2018\u2018Ayudas SEOM de Intensificaci\u00f3n para Investigadores J\u00f3venes\u2019\u2019","award":["212082PCR4056"],"award-info":[{"award-number":["212082PCR4056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A multicenter biomarker ambispective study was performed in mHSPC patients. PTEN mRNA expression was assessed by nCounter in formalin-fixed paraffin-embedded tumor samples. PTENlow status was defined by a previously validated cut-off and was correlated with castration-resistant prostate cancer (CRPC)-free survival (CRPC-FS) (primary endpoint) and overall survival (OS). RNA-Seq was performed to molecularly characterize PTENlow vs. PTENwt tumors. A total of 380 patients were included, 350 eligible. PTENlow was observed in 28.2% of patients and was independently associated with shorter CRPC-FS (HR 1.6, 95% CI 1.2\u20132.1, p = 0.002) and OS (HR 1.5, 95% CI 1.1\u20132, p = 0.014). PTENlow tumors showed overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures, reduced expression of the androgen receptor pathway, and a distinct immune microenvironment. Using microarray data from the CHAARTED trial, we developed a PTEN-low related signature, independently associated with CRPC-FS (HR 1.5, 95% CI 1\u20132.3, p = 0.036) and OS (HR 1.9, C1 1.2\u20132.9, p = 0.005), and identified targets for potential therapies in PTEN-altered tumors. We conclude that PTENlow correlates with an aggressive clinical outcome in mHSPC patients and is associated with a unique transcriptional profile. These findings further support the investigation of novel therapeutic strategies for patients with PTEN alterations.<\/jats:p>","DOI":"10.3390\/ijms26136244","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression"],"prefix":"10.3390","volume":"26","author":[{"given":"Marta","family":"Garcia de Herreros","sequence":"first","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-0426","authenticated-orcid":false,"given":"Natalia","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-5811","authenticated-orcid":false,"given":"Joan","family":"Padrosa","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Aversa","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-3357","authenticated-orcid":false,"given":"Laura","family":"Ferrer-Mileo","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-2048","authenticated-orcid":false,"given":"Samuel","family":"Garc\u00eda-Esteve","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Rodr\u00edguez-Carunchio","sequence":"additional","affiliation":[{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Pathology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-4380","authenticated-orcid":false,"given":"Isabel","family":"Trias","sequence":"additional","affiliation":[{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Pathology, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2580-1763","authenticated-orcid":false,"given":"Laia","family":"Fern\u00e1ndez-Ma\u00f1as","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Mar\u00edn-Aguilera","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Altamirano","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mazariegos","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Font","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Institut Catal\u00e0 d\u2019Oncologia, Hospital Germans Trias i Pujol, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejo","family":"Rodriguez-Vida","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Climent","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Instituto Valenciano de Oncolog\u00eda (IVO), 46009 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cros","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital General de Granollers, 08402 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-3276","authenticated-orcid":false,"given":"Isabel","family":"Chirivella","sequence":"additional","affiliation":[{"name":"Department of Medical 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Catal\u00e0 d\u2019Oncologia, 08916 Germans Trias i Pujol Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Pardo","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Institut Catal\u00e0 d\u2019Oncologia, Hospital Germans Trias i Pujol, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2377-540X","authenticated-orcid":false,"given":"Aleix","family":"Prat","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d2scar","family":"Reig","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8088-5966","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Mellado","sequence":"additional","affiliation":[{"name":"Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain"},{"name":"Medical Oncology Department, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"Uro-Oncology Unit, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. 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