Tryptophan–kynurenine ratio as a biomarker of bladder cancer

• Published in: BJU international Vol. 127; no. 4; pp. 445 - 453
• Main Authors: Lee, Sze Han, Mahendran, Ratha, Tham, Sin Mun, Thamboo, Thomas Paulraj, Chionh, Billy Jianhao, Lim, Yi Xin, Tsang, Woon Chau, Wu, Qing Hui, Chia, Jun Yang, Tay, Melissa Hui Wen, Goh, Benjamin Yen Seow, Chen, Kelven Weijing, Mallari, Jeane Zepeda, Periaswami, Revathi, Raman, Lata, Choo, Shoa Nian, Kioh, Dorinda Yan Qin, Chiong, Edmund, Esuvaranathan, Kesavan, Chan, Eric Chun Yong
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2021
• Subjects: Animal models; biomarker; Biomarkers; Bladder cancer; BladderCancer; blcsm; Cancer; Creatinine; Dioxygenase; kynurenine; Prostate; surveillance; Tryptophan; Tumors; uroonc; utuc; uroonc; blcsm; bladder cancer; kynurenine; utuc; surveillance; BladderCancer; biomarker; tryptophan
• DOI: 10.1111/bju.15205
• ISSN: 1464-4096

Objectives To investigate plasma and urinary kynurenine (KYN)–tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3‐dioxygenase 1 (IDO1) in relation to tryptophan 2,3‐dioxygenase (TDO2) in bladder tumour, and the correlation of KYN–TRP ratio with bladder tumour burden. Methods Metabotyping of the TRP–KYN metabolic axis was performed via a clinical case–control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN–TRP ratio and bladder tumour were performed using a murine orthotopic prostate‐specific antigen (PSA)‐secreting MB49 bladder cancer model. Results We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN–TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN–TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model. Conclusion Kynurenine–tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.