Abstract
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.
Highlights
Prostate cancer (PCa) is one of the tumor pathologies with the highest incidence among the male population and represents a severe health problem worldwide [1]
Patients with significant PCa (SigPCa) had significantly higher plasma prostatic specific antigen (PSA) levels compared to healthy patients and negative biopsy patients (p < 0.001), while a similar, albeit non-significant difference was found compared to patients with NonSigPCa
Considerable research efforts have been focused on the identification of novel biomarkers that could complement or even replace plasma PSA in order to improve the capacity of the clinicians to diagnose PCa
Summary
Prostate cancer (PCa) is one of the tumor pathologies with the highest incidence among the male population and represents a severe health problem worldwide [1]. The most important drawback is the compromised specificity, which is due to the fact that there are several non-tumor factors (i.e., benign prostatic hyperplasia, prostatitis) associated to an increase of PSA levels [2] For these reasons, the anatomo-pathological analysis of prostate biopsies, which represent a highly invasive technique, is still essential to appropriately diagnose PCa. the use of PSA levels as diagnostic tool for PCa is linked to many unnecessary biopsies, which are potentially associated to clinical side effects (e.g., infections, bleeding), overdiagnosis and overtreatment, leading to an increase in economic burden [3]. New biomarkers for PCa diagnosis are necessary, ideally non-invasive biomarkers with prognostic/aggressiveness and/or therapeutic potential
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