Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer
Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer
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DOI：
10.1016/j.lungcan.2009.05.001
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发表时间：
2010-03-01
期刊：
影响因子：
5.3
通讯作者：
Chida, Kingo
中科院分区：
文献类型：
--
作者：
Suzuki, Yuzo;Suda, Takafumi;Chida, Kingo
背景。吲哚胺 2,3-双加氧酶 (IDO) 催化犬尿氨酸 (Kyn) 途径中色氨酸 (Trp) 降解的限速步骤。通过消耗色氨酸，IDO 被认为是肿瘤细胞的基本免疫逃逸机制。然而，IDO在肺癌中的表达尚未得到深入研究。因此，本研究探讨了肺癌中100种通过血清Trp和Kyn浓度测定的活性以及IDO活性与临床参数之间的相关性方法采用液相色谱/电喷雾电离串联质谱（LC-ESI/MS/MS）同时测定了123例肺癌患者血清中的Trp和Kyn浓度。 肺癌和45名健康对照者的IDO活性通过计算血清Kyn与Trp比值（Kyn/Trp比率）结果来估计。肺癌患者的色氨酸浓度显着低于健康对照（分别为 62.6 +/- 15 8 muM vs 711 +/- 118 muM，p = 00007）。而患者中的 Kyn 浓度显着高于对照组（分别为 2 82 +/- 1.17 muM 和 2 30 +/- 056 muM，p = 00036）。由 Kyn/Trp 比值确定的 IDO 活性在患者中显着高于对照组（分别为 471 +/- 21 3 与 32 9 +/- 910；p < 0 0001）。此外，晚期肺癌患者的 Trp 浓度显着低于早期患者，IDO 活性显着高于早期患者（分别为 p = 0.0058 和 p = 0.0209）。增加于 肺癌患者中，较高的 IDO 活性与更晚期相关。这些结果表明，IDO 活性增加可能通过其免疫抑制作用参与肺癌的疾病进展 (C) 2009 Elsevier Ireland Ltd 版权所有。
Background. Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tiyptophan (Trp) degradation along the kynurenine (Kyn) pathway. By depleting tryptophan, IDO is considered to be a fundamental immune escape mechanism for tumor cells. However, IDO expression in lung cancer has not been explored thoroughly Thus, the present study investigated 100 activity determined by serum Trp and Kyn concentrations in lung cancer and the correlation between the IDO activity and clinical parametersMethod The concentrations of Trp and Kyn were measured simultaneously by liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) in the sera of 123 patients with lung cancer and 45 healthy controls The IDO activity was estimated by calculating the serum Kyn-to-Trp ratio (Kyn/Trp ratio)Results. Trp concentrations were significantly lower in patients with lung cancer than in healthy controls (62.6 +/- 15 8 mu M vs 711 +/- 118 mu M, respectively, p = 00007). while Kyn concentrations were significantly higher in patients compared with the controls (2 82 +/- 1.17 mu M vs 2 30 +/- 056 mu M, respectively, p = 00036). The IDO activity determined by the Kyn/Trp ratio was significantly higher in the patients than in the controls (471 +/- 21 3 vs 32 9 +/- 910, respectively; p < 0 0001) In addition, patients in the advanced stages of lung cancer had significantly lower Trp concentrations and higher IDO activity than those in the early stages (p = 0.0058 and p = 0.0209. respectively)Conclusions IDO activity was Increased in lung cancer patients, and higher IDO activity was associated with more advanced stages These results suggest that increased IDO activity is involved in disease progression of lung cancer, possibly through its immunosuppressive effect (C) 2009 Elsevier Ireland Ltd All rights reserved.