结直肠癌 (CRC) 幸存者普遍存在疲劳，影响他们的健康相关生活质量 (HRQoL)。炎症诱导的犬尿氨酸通路激活可能在癌症相关的疲劳和 HRQoL 中发挥作用，但证据很少。因此，我们的目的是研究 CRC 幸存者治疗后 12 个月内血浆色氨酸、犬尿氨酸及其比率与疲劳和 HRQoL 的纵向关联。对 249 名 I-III 期 CRC 幸存者在治疗后 6 周、6 个月和 12 个月进行了重复测量。使用液相色谱-串联质谱 (LC/MS-MS) 分析血浆色氨酸和八种犬尿氨酸。使用经过验证的问卷评估疲劳和 HRQoL 结果。采用混杂因素调整线性混合模型来分析纵向关联，并进行错误发现率 (FDR) 校正。较高的色氨酸 (Trp)、犬尿酸 (KA) 和黄尿酸 (XA) 浓度以及较高的犬尿酸与喹啉酸比率 (KA/QA) 与较少的疲劳和更好的功能相关，而较高的犬尿氨酸与色氨酸比率（KTR）和3-羟基犬尿氨酸比率（HKr）与更疲劳和更差的功能相关。最后，较高的 KA 和 XA 浓度以及较高的 KA/QA 比率与较高的 HRQoL 总体评分相关，而较高的 HKr 与较低的 HRQoL 总体评分相关。总之，我们观察到色氨酸和几种犬尿氨酸与 CRC 幸存者治疗后 12 个月的疲劳和 HRQoL 纵向相关。需要未来的研究来验证我们的研究结果，并探索犬尿氨酸途径作为减少 CRC 治疗后疲劳和提高 HRQoL 干预目标的潜力。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post-treatment were performed in 249 stage I-III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder-adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid-to-quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine-to-tryptophan ratio (KTR) and 3-hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment.© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.