Klotho in Cancer: Potential Diagnostic and Prognostic Applications
Jucileide Mota,
Alice Marques Moreira Lima,
Jhessica I. S. Gomes,
Marcelo Souza de Andrade,
Haissa O. Brito,
Melaine M. A. Lawall Silva,
Ana I. Faustino-Rocha,
Paula A. Oliveira,
Fernanda F. Lopes,
Rui M. Gil da Costa
Affiliations
Jucileide Mota
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Alice Marques Moreira Lima
Health Sciences Center, State University of the Tocantins Region of Maranhão (UEMASUL), Imperatriz 6591-480, Brazil
Jhessica I. S. Gomes
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Marcelo Souza de Andrade
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Haissa O. Brito
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Melaine M. A. Lawall Silva
Morphology Department, Federal University of Maranhão, São Luís 65085-580, Brazil
Ana I. Faustino-Rocha
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Paula A. Oliveira
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Fernanda F. Lopes
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Rui M. Gil da Costa
Post-Graduate Programme in Adult Health (PPGSAD), Federal University of Maranhão, São Luís 65085-580, Brazil
Klotho proteins, αKlotho, βKlotho, and γKlotho, 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. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho 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.
