Tryptophan/kynurenine ratio as biomarker of bladder cancer

Objectives: To investigate plasma and urinary kynurenine/tryptophan (KYN/TRP) ratio in bladder cancer, expression of indoleamine 2,3-dioxygenase 1 (IDO1) vis-à-vis tryptophan 2,3-dioxygenase (TDO2) in bladder tumor and correlation of KYN/TRP ratio with bladder tumor burden.

Methods: Metabotyping of 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 tumor 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 tumor. We reported the positive correlation between IDO1 expression, KYN/TRP ratio, normalized PSA to creatinine (CR) (PSA/CR) and bladder tumor burden in the murine model.

Conclusion: KYN/TRP ratio is promising surveillance biomarker for bladder cancer but would require further validation before clinical translation is possible.

Keywords: biomarker; bladder cancer; kynurenine; surveillance; tryptophan.