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Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

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Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), 14004 Córdoba, Spain
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Department of Cell Biology, Physiology, and Immunology, University of Córdoba, 14071 Córdoba, Spain
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Hospital Universitario Reina Sofía (HURS), 14004 Córdoba, Spain
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Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, (CIBERobn), 14004 Córdoba, Spain
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Urology Service, HURS/IMIBIC, 14004 Córdoba, Spain
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Anatomical Pathology Service, HURS, 14004 Córdoba, Spain
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Department of Innovation and Methodology, IMIBIC, 14004 Córdoba, Spain
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Oncology Department, IMIBIC, 14004 Córdoba, Spain
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Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, 14004 Córdoba, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(12), 2056; https://doi.org/10.3390/jcm8122056
Received: 15 October 2019 / Revised: 18 November 2019 / Accepted: 19 November 2019 / Published: 22 November 2019
(This article belongs to the Section Endocrinology & Metabolism)
Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa. View Full-Text
Keywords: GOAT-enzyme; prostate cancer; diagnosis; therapy; PSA GOAT-enzyme; prostate cancer; diagnosis; therapy; PSA
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Jiménez-Vacas, J.M.; Gómez-Gómez, E.; Montero-Hidalgo, A.J.; Herrero-Aguayo, V.; L-López, F.; Sánchez-Sánchez, R.; Guler, I.; Blanca, A.; Méndez-Vidal, M.J.; Carrasco, J.; Lopez-Miranda, J.; Requena-Tapia, M.J.; Castaño, J.P.; Gahete, M.D.; Luque, R.M. Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer. J. Clin. Med. 2019, 8, 2056.

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