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Noninvasive Serum Metabolomic Profiling Reveals Elevated Kynurenine Pathway's Metabolites in Humans with Prostate Cancer

Authors
 Adnan Khan  ;  Soo An Choi  ;  Jinhyuk Na  ;  Aryo Dimas Pamungkas  ;  Keum Ji Jung  ;  Sun Ha Jee  ;  Youngja H. Park 
Citation
 JOURNAL OF PROTEOME RESEARCH, Vol.18(4) : 1532-1541, 2019 
Journal Title
 JOURNAL OF PROTEOME RESEARCH 
ISSN
 1535-3893 
Issue Date
2019
Keywords
biomarker ; kynurenine ; liquid chromatography ; metabolomics ; prostate cancer
Abstract
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.
Full Text
https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00803
DOI
10.1021/acs.jproteome.8b00803
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174747
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