Evaluation of kynurenine and tryptophan metabolism in bladder cancer: Diagnostic and prognostic implications of IDO1 polymorphism.

OBJECTIVE

The tryptophan-kynurenine (TRP-KYN) pathway, regulated by indoleamine 2,3-dioxygenase 1 (IDO1), plays a pivotal role in tumor immune escape. Altered TRP catabolism and IDO1 gene polymorphisms may influence bladder cancer (BC) behavior through immune metabolic mechanisms. To evaluate the diagnostic and prognostic value of plasma and urinary KYN/TRP ratios and the IDO1 rs10089084 (G > C) polymorphism in patients with BC.

METHODS

In this case-control study, plasma and urine samples were obtained from 58 patients with BC and 70 healthy controls before diagnostic cystoscopy. TRP and KYN levels were quantified by high-performance liquid chromatography. IDO1 rs10089084 genotypes were determined via PCR-RFLP. Diagnostic accuracy was assessed by ROC analysis, and recurrence risk was analyzed using Cox regression.

RESULTS

Plasma KYN/TRP ratios were significantly higher in BC patients than in controls (P = 0.011; AUC = 0.617). Among BC cases, the urinary KYN/TRP ratio discriminated patients with a visible bladder mass (AUC = 0.879; 95% CI 0.774-0.984; cut-off = 0.0895; sensitivity = 100%; specificity = 70.8%). In recurrence analysis, the IDO1 rs10089084 C allele independently predicted recurrence risk (HR = 7.51; 95% CI 1.70-33.10; P = 0.008). No association was found with progression.

CONCLUSIONS

Combined metabolic and genetic profiling implicates the IDO1-TRP-KYN axis in BC pathophysiology. Urinary KYN/TRP ratio offers a noninvasive, biologically grounded marker for intravesical tumor activity, while the IDO1 rs10089084 variant provides complementary prognostic information. These findings support the integration of immunometabolic biomarkers into risk-adapted surveillance strategies.