Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer
Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer
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DOI：
10.3390/jcm8122056
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发表时间：
2019-12-01
影响因子：
3.9
通讯作者：
Luque, Raul M.
中科院分区：
文献类型：
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作者：
Jimenez-Vacas, Juan M.;Gomez-Gomez, Enrique;Luque, Raul M.
最近的数据表明，血浆Ghrelin o -酰基转移酶（GOAT）水平可能是前列腺癌（PCa）的一种新的诊断生物标志物。在这项研究中，我们旨在探讨尿中山羊的诊断和预后/侵袭能力，并询问其在前列腺癌中的假定病理生理作用。我们分析了993例患者的尿/血浆GOAT水平。在体外（即细胞增殖）和体内（异种移植模型中的肿瘤生长）方法中，对PCa细胞中GOAT表达/活性的调节进行了响应。我们的研究结果表明，与对照组相比，PCa患者的血浆和尿液中GOAT水平显著升高。值得注意的是，GOAT在诊断PCa方面明显优于PSA，在PSA水平为3至10 ng/mL（所谓的PSA灰色地带）的患者中，GOAT的诊断效果明显优于PSA。此外，尿GOAT水平与临床（如gleason评分、PSA水平）和分子（如CDK2/CDK6/CDKN2A表达）侵袭性参数相关。事实上，在PCa细胞中，GOAT过表达增加，而其沉默/阻断降低了细胞增殖。此外，来自goat过表达PCa （DU145）细胞的异种移植物肿瘤的发生率明显高于来自模拟过表达细胞的肿瘤。总之，我们的研究结果表明，山羊可以作为尿中的诊断和侵袭性标志物，也可以作为前列腺癌的治疗靶点。
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.