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proteins, \u03b1Klotho, \u03b2Klotho, and \u03b3Klotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. \u03b1Klotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble \u03b1Klotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. \u03b3Klotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and \u03b2Klotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.<\/jats:p>","DOI":"10.3390\/diagnostics13213357","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:48:31Z","timestamp":1698756511000},"page":"3357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Klotho in Cancer: Potential Diagnostic and Prognostic Applications"],"prefix":"10.3390","volume":"13","author":[{"given":"Jucileide","family":"Mota","sequence":"first","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"given":"Alice Marques Moreira","family":"Lima","sequence":"additional","affiliation":[{"name":"Health Sciences Center, State University of the Tocantins Region of Maranh\u00e3o (UEMASUL), Imperatriz 6591-480, Brazil"}]},{"given":"Jhessica I. S.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8518-6910","authenticated-orcid":false,"given":"Marcelo","family":"Souza de Andrade","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"given":"Haissa O.","family":"Brito","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"},{"name":"Morphology Department, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-1612","authenticated-orcid":false,"given":"Melaine M. A. Lawall","family":"Silva","sequence":"additional","affiliation":[{"name":"Morphology Department, Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5572-6317","authenticated-orcid":false,"given":"Ana I.","family":"Faustino-Rocha","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Inov4Agro\u2014Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Inov4Agro\u2014Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-412X","authenticated-orcid":false,"given":"Fernanda F.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui M.","family":"Gil da Costa","sequence":"additional","affiliation":[{"name":"Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranh\u00e3o, S\u00e3o Lu\u00eds 65085-580, Brazil"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Inov4Agro\u2014Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"Associate Laboratory in Chemical Engineering, Faculty of Engineering (ALiCE), University of Porto, 4200-465 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Health Research Network, Research Center of Portuguese Oncology Institute of Porto (CIIPOP\/RISE@CIIPOP), 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro","year":"1997","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1006\/bbrc.1997.8019","article-title":"Identification of the HumanKlothoGene and Its Two Transcripts Encoding Membrane and SecretedKlothoProtein","volume":"242","author":"Matsumuraab","year":"1998","journal-title":"Biochem. 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