Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites
Human Prostate Cancer Is Characterized by an Increase in Urea Cycle Metabolites
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人类前列腺癌的特点是尿素循环代谢物增加
DOI：
10.3390/cancers12071814
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发表时间：
2020-07-01
期刊：
影响因子：
5.2
通讯作者：
Lutz, Stefan Z.
中科院分区：
文献类型：
--
作者：
Franko, Andras;Shao, Yaping;Lutz, Stefan Z.
尽管前列腺癌是男性中最常见的癌症类型，但导致前列腺癌（PCa）的病理生理机制仍未得到充分了解。据推测，线粒体代谢改变在前列腺癌的发生发展中发挥一定作用。为确定关键代谢物（包括线粒体致癌代谢物），研究人员采用毛细管电泳和液相色谱 - 质谱联用技术，对前列腺癌患者的良性前列腺组织和癌组织进行了分析，并利用实时聚合酶链反应（PCR）研究了基因表达情况。在前列腺癌组织中，研究人员发现三羧酸循环早期代谢物水平降低，而尿素循环代谢物（包括天冬氨酸、精氨琥珀酸、精氨酸、脯氨酸）以及致癌代谢物富马酸的含量高于良性对照组。富马酸含量与致癌的缺氧诱导因子1α（HIF1α）和核因子κB（NFκB）通路的基因表达呈正相关，且前列腺癌样本中这些通路的基因表达显著高于良性对照组。此外，来自癌症基因组图谱（TCGA）数据库的数据表明，NFκB通路激活的前列腺癌患者生存率较低。总之，研究数据显示富马酸含量与致癌基因呈正相关。
Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes.