{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:31:29Z","timestamp":1768483889338,"version":"3.49.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomark Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions.<\/jats:p><jats:p>Ki67 immunoscore, <jats:italic>GSTP1<\/jats:italic> and <jats:italic>KLF8<\/jats:italic> promoter methylation levels (<jats:sup>me<\/jats:sup>) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms).<\/jats:p><jats:p>Higher Ki67 index correlated with worse BCR-free survival, whereas higher <jats:italic>KLF8<\/jats:italic><jats:sup><jats:italic>me<\/jats:italic><\/jats:sup> levels were associated with improved overall survival, especially in patients with lower-grade tumors. <jats:italic>GSTP1<\/jats:italic><jats:sup><jats:italic>me<\/jats:italic><\/jats:sup> levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator \u2013 ProstARK (including Ki67 and clinicopathologic parameters) \u2013 disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability.<\/jats:p><jats:p>Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results.<\/jats:p>","DOI":"10.1186\/s40364-024-00627-4","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T17:02:37Z","timestamp":1722531757000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Redefining prostate cancer risk stratification: a pioneering strategy to estimate outcome based on Ki67 immunoscoring"],"prefix":"10.1186","volume":"12","author":[{"given":"\u00c2ngela","family":"Albuquerque-Castro","sequence":"first","affiliation":[]},{"given":"Catarina","family":"Macedo-Silva","sequence":"additional","affiliation":[]},{"given":"R\u00faben","family":"Oliveira-Sousa","sequence":"additional","affiliation":[]},{"given":"Vera","family":"Const\u00e2ncio","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Lobo","sequence":"additional","affiliation":[]},{"given":"Isa","family":"Carneiro","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"issue":"4","key":"627_CR1","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.cell.2015.10.025","volume":"163","author":"The Molecular Taxonomy of Primary Prostate Cancer","year":"2015","unstructured":"The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015;163(4):1011\u201325.","journal-title":"Cell"},{"key":"627_CR2","unstructured":"Health Quality Ontario. Prolaris Cell Cycle Progression Test for Localized Prostate Cancer: A Health Technology Assessment. Ont Health Technol Assess Ser. 2017;17(6):1\u201375."},{"issue":"12","key":"627_CR3","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1093\/jnci\/djp122","volume":"101","author":"MR Cooperberg","year":"2009","unstructured":"Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101(12):878\u201387.","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"627_CR4","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.eururo.2012.05.072","volume":"62","author":"MA Dall'Era","year":"2012","unstructured":"Dall\u2019Era MA, Albertsen PC, Bangma C, Carroll PR, Carter HB, Cooperberg MR, et al. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol. 2012;62(6):976\u201383.","journal-title":"Eur Urol"},{"issue":"1","key":"627_CR5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s00345-021-03622-8","volume":"40","author":"CH Walker","year":"2022","unstructured":"Walker CH, Marchetti KA, Singhal U, Morgan TM. Active surveillance for prostate cancer: selection criteria, guidelines, and outcomes. World J Urol. 2022;40(1):35\u201342.","journal-title":"World J Urol"},{"key":"627_CR6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S0091-679X(01)64022-6","volume":"64","author":"MG Daidone","year":"2001","unstructured":"Daidone MG, Costa A, Silvestrini R. Cell proliferation markers in human solid tumors: assessing their impact in clinical oncology. 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Urol Oncol. 2018;36(4):161.e7-.e17.","DOI":"10.1016\/j.urolonc.2017.10.028"},{"issue":"2","key":"627_CR11","doi-asserted-by":"publisher","first-page":"87","DOI":"10.4081\/ejh.2020.3098","volume":"64","author":"S Ziaran","year":"2020","unstructured":"Ziaran S, Harsanyi S, Bevizova K, Varchulova Novakova Z, Trebaticky B, Bujdak P, et al. Expression of E-cadherin, Ki-67, and p53 in urinary bladder cancer in relation to progression, survival, and recurrence. Eur J Histochem. 2020;64(2):87\u201394.","journal-title":"Eur J Histochem."},{"key":"627_CR12","doi-asserted-by":"publisher","first-page":"175628722211039","DOI":"10.1177\/17562872221103988","volume":"14","author":"MW Farha","year":"2022","unstructured":"Farha MW, Salami SS. Biomarkers for prostate cancer detection and risk stratification. Ther Adv Urol. 2022;14:17562872221103988.","journal-title":"Ther Adv Urol"}],"updated-by":[{"DOI":"10.1186\/s40364-024-00670-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000}}],"container-title":["Biomarker Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-024-00627-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40364-024-00627-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40364-024-00627-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T15:14:48Z","timestamp":1729005288000},"score":1,"resource":{"primary":{"URL":"https:\/\/biomarkerres.biomedcentral.com\/articles\/10.1186\/s40364-024-00627-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["627"],"URL":"https:\/\/doi.org\/10.1186\/s40364-024-00627-4","relation":{},"ISSN":["2050-7771"],"issn-type":[{"value":"2050-7771","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,1]]},"assertion":[{"value":"13 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s40364-024-00670-1","URL":"https:\/\/doi.org\/10.1186\/s40364-024-00670-1","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by IPO Porto Institutional Review Board (CES86\/2022) and conformed to all the Portuguese laws.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"75"}}