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Tryptophan–kynurenine ratio as a biomarker of bladder cancer
Author(s) -
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
Publication year - 2021
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.15205
Subject(s) - kynurenine , tryptophan , bladder cancer , biomarker , urinary system , kynurenine pathway , urinary bladder , cancer , medicine , chemistry , tryptophan metabolism , prostate cancer , creatinine , urology , oncology , cancer research , biochemistry , amino acid
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.