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Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway's Metabolites in Humans with Prostate Cancer.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-01-22 , DOI: 10.1021/acs.jproteome.8b00803
Adnan Khan 1 , Soo An Choi 2 , Jinhyuk Na 1 , Aryo Dimas Pamungkas 1 , Keum Ji Jung 3 , Sun Ha Jee 3 , Youngja H Park 1
Affiliation  

This study aimed to apply high-resolution metabolomics to detect compounds that may contribute significantly to prostate cancer (PCa) development. The test population's sera for evaluating the metabolic differences consisted of healthy control ( n = 96) and PCa ( n = 50) groups. PCa patients were further divided into two groups based on whether their PSA level was >4 ( n = 25) or <4 ( n = 25). Univariate analysis was performed with the false discovery rate (FDR) at q = 0.05 to determine significantly different metabolites. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) clearly distinguished healthy subjects from PCa groups, while no significant difference was observed in PCa patients with PSA level < 4 or > 4. Mummichog, in combination with the KEGG and MetaboAnalyst, showed that tryptophan metabolism along the kynurenine pathway was most significantly enriched, with -log ( p) < 0.05. l-Tryptophan, kynurenine, anthranilate, isophenoxazine, glutaryl-CoA, ( S)-3-hydroxybutanoyl-CoA, acetoacetyl-CoA, and acetyl-CoA were upregulated in correlation with the PSA level of PCa patients; in contrast, indoxyl, indolelactate, and indole-3-ethanol, involved in the alternative pathway, were downregulated in the PCa patients. Validation and quantification of potential metabolites by MS/MS further confirmed the disruption of tryptophan, kynurenine, and anthranilate, suggesting that the metabolites of this pathway are potential biomarkers in patients with PCa.

中文翻译:

非侵入性血清代谢组学分析揭示了前列腺癌患者中Kynurenine途径的代谢产物升高。

这项研究旨在应用高分辨率代谢组学来检测可能对前列腺癌(PCa)发育有重大贡献的化合物。测试人群评估代谢差异的血清包括健康对照组(n = 96)和PCa(n = 50)组。PCa患者根据其PSA水平是> 4(n = 25)还是<4(n = 25)进一步分为两组。以q = 0.05的错误发现率(FDR)进行单变量分析,以确定明显不同的代谢物。主成分分析(PCA)和层次聚类分析(HCA)清楚地区分了健康人群与PCa组,而PSA水平<4或> 4的PCa患者中未观察到显着差异。Mummichog与KEGG和MetaboAnalyst结合使用,结果表明,沿犬尿氨酸途径的色氨酸代谢最显着富集,-log(p)<0.05。l-色氨酸,犬尿氨酸,邻氨基苯甲酸,异吩恶嗪,戊二酰辅酶A,(S)-3-羟基丁酰辅酶A,乙酰乙酰辅酶A和乙酰辅酶A与PCa患者的PSA水平相关。相反,在PCa患者中,替代途径中涉及的吲哚酚,吲哚丙酸酯和吲哚-3-乙醇被下调。MS / MS对潜在代谢物的验证和定量进一步证实了色氨酸,犬尿氨酸和邻氨基苯甲酸的破坏,这表明该途径的代谢物是PCa患者的潜在生物标志物。(S)-3-羟基丁酰辅酶A,乙酰乙酰辅酶A和乙酰辅酶A与PCa患者的PSA水平相关。相反,在PCa患者中,替代途径中涉及的吲哚酚,吲哚丙酸酯和吲哚-3-乙醇被下调。MS / MS对潜在代谢物的验证和定量进一步证实了色氨酸,犬尿氨酸和邻氨基苯甲酸的破坏,这表明该途径的代谢物是PCa患者的潜在生物标志物。(S)-3-羟基丁酰辅酶A,乙酰乙酰辅酶A和乙酰辅酶A与PCa患者的PSA水平相关。相反,在PCa患者中,替代途径中涉及的吲哚酚,吲哚丙酸酯和吲哚-3-乙醇被下调。MS / MS对潜在代谢物的验证和定量进一步证实了色氨酸,犬尿氨酸和邻氨基苯甲酸的破坏,这表明该途径的代谢物是PCa患者的潜在生物标志物。
更新日期:2019-02-07
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