Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression.
Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression.
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DOI：
10.1080/20013078.2018.1470442
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发表时间：
2018
影响因子：
16
通讯作者：
Falcón-Pérez JM
中科院分区：
文献类型：
--
作者：
Clos-Garcia M;Loizaga-Iriarte A;Zuñiga-Garcia P;Sánchez-Mosquera P;Rosa Cortazar A;González E;Torrano V;Alonso C;Pérez-Cormenzana M;Ugalde-Olano A;Lacasa-Viscasillas I;Castro A;Royo F;Unda M;Carracedo A;Falcón-Pérez JM
尿液含有细胞外囊泡（EV），可浓缩分子并保护它们免受降解。因此，尿EV的分离和表征可以提高生物标志物发现的效率。我们先前已经鉴定了与良性前列腺增生（BPH）相比，前列腺癌（PCa）患者的尿EV中具有差异丰度的蛋白质和RNA。在这里，我们重点分析了从PCa和BPH患者中收集的尿液EV中所含的代谢物。采用超高效液相色谱-质谱联用技术对EV进行靶向代谢组学分析。研究了代谢物与临床参数之间的相关性，并检测了PCa尿EV中具有差异丰度的代谢物，并将其映射到细胞途径中。我们检测到248属于不同的化学家族，包括氨基酸和各种脂质物质的代谢产物。在这些代谢物中，76个在PCa和BPH之间表现出显著的差异丰度。有趣的是，尿液EV重现了PCa中报告的许多代谢改变，包括磷脂酰胆碱、酰基肉毒碱、柠檬酸盐和犬尿氨酸。重要的是，我们发现PCa尿EV中类固醇激素3 β-羟基雄酮-5-烯-17-酮-3-硫酸盐（硫酸脱氢表雄酮）水平升高，与这种类型癌症中雄激素合成的潜在升高一致。这项工作支持尿EV作为推断PCa代谢变化的非侵入性来源。
Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultra-high-performance liquid chromatography–mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa.
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影响因子：
3.6
作者：
Gonzalez, Esperanza;van Liempd, Sebastiaan;Conde-Vancells, Javier;Gutierrez-de Juan, Virginia;Perez-Cormenzana, Miriam;Mayo, Rebeca;Berisa, Agustin;Alonso, Cristina;Marquez, Cesar A.;Barr, Jonathan;Lu, Shelly C.;Mato, Jose M.;Falcon-Perez, Juan M.
通讯作者：
Falcon-Perez, Juan M.
影响因子：
14.8
作者：
Iraci N;Gaude E;Leonardi T;Costa ASH;Cossetti C;Peruzzotti-Jametti L;Bernstock JD;Saini HK;Gelati M;Vescovi AL;Bastos C;Faria N;Occhipinti LG;Enright AJ;Frezza C;Pluchino S
通讯作者：
Pluchino S
影响因子：
4.4
作者：
Barr J;Caballería J;Martínez-Arranz I;Domínguez-Díez A;Alonso C;Muntané J;Pérez-Cormenzana M;García-Monzón C;Mayo R;Martín-Duce A;Romero-Gómez M;Lo Iacono O;Tordjman J;Andrade RJ;Pérez-Carreras M;Le Marchand-Brustel Y;Tran A;Fernández-Escalante C;Arévalo E;García-Unzueta M;Clement K;Crespo J;Gual P;Gómez-Fleitas M;Martínez-Chantar ML;Castro A;Lu SC;Vázquez-Chantada M;Mato JM
通讯作者：
Mato JM
影响因子：
4.1
作者：
Monteiro, M. S.;Carvalho, M.;Guedes de Pinho, P.
通讯作者：
Guedes de Pinho, P.
影响因子：
6.4
作者：
CHAUDRY, AA;WAHLE, KWJ;MOFFAT, LEF
通讯作者：
MOFFAT, LEF