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

• Published in: Journal of proteome research 2019-04, Vol.18 (4), p.1532-1541
• Main Authors: Khan, Adnan, Choi, Soo An, Na, Jinhyuk, Pamungkas, Aryo Dimas, Jung, Keum Ji, Jee, Sun Ha, Park, Youngja H
• Format: Article
• Language: English
• ISSN: 1535-3893; 1535-3907
• DOI: 10.1021/acs.jproteome.8b00803

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. 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.