{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:50:13Z","timestamp":1790761813961,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["FISS-21-RD21\/0002\/0041"],"award-info":[{"award-number":["FISS-21-RD21\/0002\/0041"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PT20\/00161"],"award-info":[{"award-number":["PT20\/00161"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PT23\/00077"],"award-info":[{"award-number":["PT23\/00077"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["SEK-25-GRU-GIC-24-069"],"award-info":[{"award-number":["SEK-25-GRU-GIC-24-069"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["FPU20\/06016"],"award-info":[{"award-number":["FPU20\/06016"]}]},{"name":"Agencia de Ciencia, Competitividad Empresarial e Innovacion Asturiana","award":["FISS-21-RD21\/0002\/0041"],"award-info":[{"award-number":["FISS-21-RD21\/0002\/0041"]}]},{"name":"Agencia de Ciencia, Competitividad Empresarial e Innovacion Asturiana","award":["PT20\/00161"],"award-info":[{"award-number":["PT20\/00161"]}]},{"name":"Agencia de Ciencia, Competitividad Empresarial e Innovacion Asturiana","award":["PT23\/00077"],"award-info":[{"award-number":["PT23\/00077"]}]},{"name":"Agencia de Ciencia, Competitividad Empresarial e Innovacion Asturiana","award":["SEK-25-GRU-GIC-24-069"],"award-info":[{"award-number":["SEK-25-GRU-GIC-24-069"]}]},{"name":"Agencia de Ciencia, Competitividad Empresarial e Innovacion Asturiana","award":["FPU20\/06016"],"award-info":[{"award-number":["FPU20\/06016"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","award":["FISS-21-RD21\/0002\/0041"],"award-info":[{"award-number":["FISS-21-RD21\/0002\/0041"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","award":["PT20\/00161"],"award-info":[{"award-number":["PT20\/00161"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","award":["PT23\/00077"],"award-info":[{"award-number":["PT23\/00077"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","award":["SEK-25-GRU-GIC-24-069"],"award-info":[{"award-number":["SEK-25-GRU-GIC-24-069"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","award":["FPU20\/06016"],"award-info":[{"award-number":["FPU20\/06016"]}]},{"name":"Spanish Ministry of Universities","award":["FISS-21-RD21\/0002\/0041"],"award-info":[{"award-number":["FISS-21-RD21\/0002\/0041"]}]},{"name":"Spanish Ministry of Universities","award":["PT20\/00161"],"award-info":[{"award-number":["PT20\/00161"]}]},{"name":"Spanish Ministry of Universities","award":["PT23\/00077"],"award-info":[{"award-number":["PT23\/00077"]}]},{"name":"Spanish Ministry of Universities","award":["SEK-25-GRU-GIC-24-069"],"award-info":[{"award-number":["SEK-25-GRU-GIC-24-069"]}]},{"name":"Spanish Ministry of Universities","award":["FPU20\/06016"],"award-info":[{"award-number":["FPU20\/06016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism and mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma and resected brain metastases who underwent curative treatment between 2007 and 2017 and evaluated their prognostic significance. Tissue microarrays of primary tumors and matched metastases were analyzed using the H-score method. PI3K expression was significantly higher in primary tumors (96.8 \u00b1 57.9 vs. 43.5 \u00b1 62.3; p = 0.003) and in stage IV adenocarcinomas (113.3 \u00b1 56.3 vs. 61.4 \u00b1 47.1; p = 0.043). PINK1 expression showed no significant variation across disease stages. Univariate analysis identified older age (&gt;55 years), PI3K overexpression (HR = 7.791, 95% CI 1.718\u201336.432; &gt;50 points), and PINK1 overexpression (&gt;100 points) in primary tumors as predictors of poor overall survival (HR = 2.236, 95% CI 1.109\u20134.508; p = 0.025). Multivariate analysis confirmed PINK1 overexpression in primary tumors as an independent prognostic factor (HR = 4.328, 95% CI 1.264\u201314.814; p = 0.020). These findings suggest that PI3K and PINK1 may serve as prognostic biomarkers in lung adenocarcinoma with resected brain metastases, emphasizing the need for research on their role in tumor progression and therapeutic response.<\/jats:p>","DOI":"10.3390\/ijms26072945","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:01:50Z","timestamp":1742817710000},"page":"2945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PI3K and PINK1 Immunoexpression as Predictors of Survival in Patients Undergoing Resection of Brain Metastases from Lung Adenocarcinoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-244X","authenticated-orcid":false,"given":"Miriam","family":"Rubiera-Vald\u00e9s","sequence":"first","affiliation":[{"name":"Department of Pathology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-4498","authenticated-orcid":false,"given":"M\u00aa Daniela","family":"Corte-Torres","sequence":"additional","affiliation":[{"name":"Biobank of Principality of Asturias (BioPA), 33011 Oviedo, Spain"},{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Navarro-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Biobank of Principality of Asturias (BioPA), 33011 Oviedo, Spain"},{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-0493","authenticated-orcid":false,"given":"Noelia","family":"Blanco-Agud\u00edn","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Department of Functional Biology, University of Oviedo, 33006 Oviedo, Spain"},{"name":"Instituto Universitario Fern\u00e1ndez-Vega, Universidad de Oviedo, 33012 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Fern\u00e1ndez-Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Biobank of Principality of Asturias (BioPA), 33011 Oviedo, Spain"},{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Department of Neurology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin M.","family":"Pi\u00f1a-Batista","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-3522","authenticated-orcid":false,"given":"Jorge","family":"Santos-Juanes","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Merayo-Lloves","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Instituto Universitario Fern\u00e1ndez-Vega, Universidad de Oviedo, 33012 Oviedo, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, University of Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-3762","authenticated-orcid":false,"given":"Luis M.","family":"Quir\u00f3s","sequence":"additional","affiliation":[{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Department of Functional Biology, University of Oviedo, 33006 Oviedo, Spain"},{"name":"Instituto Universitario Fern\u00e1ndez-Vega, Universidad de Oviedo, 33012 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-8614","authenticated-orcid":false,"given":"Adela A.","family":"Fern\u00e1ndez-Velasco","sequence":"additional","affiliation":[{"name":"Department of Pathology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Biobank of Principality of Asturias (BioPA), 33011 Oviedo, Spain"},{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, University of Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-6493","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Fern\u00e1ndez-Vega","sequence":"additional","affiliation":[{"name":"Department of Pathology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain"},{"name":"Biobank of Principality of Asturias (BioPA), 33011 Oviedo, Spain"},{"name":"Health Research Institute of the Principality of Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Instituto Universitario Fern\u00e1ndez-Vega, Universidad de Oviedo, 33012 Oviedo, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, University of Oviedo, 33006 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN 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