Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and its levels are associated with patient's metabolic status: Potential value as a non-invasive biomarker
Ghrelin O-acyltransferase (GOAT) enzyme is overexpressed in prostate cancer, and its levels are associated with patient's metabolic status: Potential value as a non-invasive biomarker
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DOI：
10.1016/j.canlet.2016.09.022
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发表时间：
2016-12-01
期刊：
影响因子：
9.7
通讯作者：
Luque, Raul M.
中科院分区：
文献类型：
--
作者：
Hormaechea-Agulla, Daniel;Gomez-Gomez, Enrique;Luque, Raul M.
Ghrelin-O-酰基转移酶（GOAT）是调节ghrelin活性的关键酶，已被认为是肥胖/糖尿病的潜在治疗靶点，也是某些内分泌相关癌症的生物标志物。然而，GOAT的存在及其在前列腺癌（PCa）中的假定作用在很大程度上尚不清楚。在这里，我们首次证明，与匹配的对照组[健康前列腺组织（n = 12）和BMI匹配对照组的血浆/尿液样本（n = 28）]相比，PCa患者的前列腺组织（n = 52）和血浆/尿液样本（n = 85）中GOAT过表达（mRNA/蛋白质水平）。有趣的是，PCA患者的GOAT水平与攻击性和代谢状况（即糖尿病）相关。实际上，GOAT的表达在培养的正常前列腺细胞和PCa细胞系中受到代谢输入（即In 1-ghrelin、胰岛素/IGF-I）的调节。重要的是，ROC曲线分析揭示了GOAT在组织/血浆/尿液水平以高灵敏度/特异性区分PCa的有价值的诊断潜力，特别是在非糖尿病个体中。此外，我们发现GOAT是由PCa细胞分泌的，并且其水平在刺激后按摩与按摩前前列腺测试的尿样中更高。总之，血浆GOAT水平与其他PCa生物标志物相比，表现出预测PCa存在的高特异性/敏感性，特别是在非糖尿病个体中，表明GOAT具有作为新型非侵入性PCa生物标志物的潜力。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Ghrelin-O-acyltransferase (GOAT) is the key enzyme regulating ghrelin activity, and has been proposed as a potential therapeutic target for obesity/diabetes and as a biomarker in some endocrine-related cancers. However, GOAT presence and putative role in prostate-cancer (PCa) is largely unknown. Here, we demonstrate, for the first time, that GOAT is overexpressed (mRNA/protein-level) in prostatic tissues (n = 52) and plasma/urine-samples (n = 85) of PCa-patients, compared with matched controls [healthy prostate tissues (n = 12) and plasma/urine-samples from BMI-matched controls (n = 28), respectively]. Interestingly, GOAT levels in PCa-patients correlated with aggressiveness and metabolic conditions (i.e. diabetes). Actually, GOAT expression was regulated by metabolic inputs (i.e. In1-ghrelin, insulin/IGF-I) in cultured normal prostate cells and PCa-cell lines. Importantly, ROC-curve analysis unveiled a valuable diagnostic potential for GOAT to discriminate PCa at the tissue/plasma/urine-level with high sensitivity/specificity, particularly in non-diabetic individuals. Moreover, we discovered that GOAT is secreted by PCa-cells, and that its levels are higher in urine samples from a stimulated post-massage vs. pre-massage prostate-test. In conclusion, plasmatic GOAT levels exhibit high specificity/sensitivity to predict PCa-presence compared with other PCa-biomarkers, especially in non-diabetic individuals, suggesting that GOAT holds potential as a novel non-invasive PCa-biomarker. (C) 2016 Elsevier Ireland Ltd. All rights reserved.