Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.
Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.
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DOI：
10.3349/ymj.2016.57.4.865
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发表时间：
2016-07
影响因子：
2.4
通讯作者：
Kim WJ
中科院分区：
文献类型：
--
作者：
Kim WT;Yun SJ;Yan C;Jeong P;Kim YH;Lee IS;Kang HW;Park S;Moon SK;Choi YH;Choi YD;Kim IY;Kim J;Kim WJ
我们先前的高效液相色谱-四极杆飞行时间质谱研究确定了膀胱癌（BCA）特异性尿液代谢物，包括肉毒碱，酰基肉毒碱和褪黑激素。本研究的目的是根据我们先前确定的尿代谢组，确定BCA中哪些代谢途径受到干扰。共分析了来自健康志愿者的135份主要BCA样本和26份对照组织样本。分析尿中特定代谢物与其相关编码基因的关联。与健康对照组相比，BCA患者的尿液标本中检测到肉毒碱-酰基肉毒碱和色氨酸代谢途径的显著改变。在我们的BCA队列（n=135）中，通过RT-PCR评估了参与肉毒碱-酰基肉毒碱代谢途径（CPT 1A、CPT 1B、CPT 1C、CPT 2、SLC 25 A20和CRAT）或色氨酸代谢（TPH 1和IDO 1）的8个基因的表达。与正常膀胱组织相比，非肌层浸润性BCA患者的肿瘤组织中CPT 1B、CPT 1C、SLC 25 A20、CRAT、TPH 1和IOD 1显著下调（p<0.05），而肌层浸润性BCA患者的CPT 1B、CPT 1C、CRAT和TPH 1下调（p<0.05），IDO 1表达无变化。与肉毒碱-酰基肉毒碱和色氨酸代谢途径相关的基因表达的改变，这是BCA中最受干扰的途径，进行了测定。
Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.