Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Hanadayama Higashiku, Hamamatsu, Shizuoka 431-3125, Japan.
Lung Cancer. 2010 Mar;67(3):361-5. doi: 10.1016/j.lungcan.2009.05.001. Epub 2009 May 31.
Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step of tryptophan (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 IDO activity determined by serum Trp and Kyn concentrations in lung cancer and the correlation between the IDO activity and clinical parameters.
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).
Trp concentrations were significantly lower in patients with lung cancer than in healthy controls (62.6+/-15.8microM vs. 71.1+/-11.8microM, respectively; p=0.0007), while Kyn concentrations were significantly higher in patients compared with the controls (2.82+/-1.17microM vs. 2.30+/-0.56microM, respectively; p=0.0036). The IDO activity determined by the Kyn/Trp ratio was significantly higher in the patients than in the controls (47.1+/-21.3 vs. 32.9+/-9.10, 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).
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.
吲哚胺 2,3-双加氧酶（IDO）催化色氨酸（Trp）沿犬尿氨酸（Kyn）途径降解的限速步骤。通过耗尽色氨酸，IDO 被认为是肿瘤细胞基本的免疫逃逸机制。然而，肺癌中 IDO 的表达尚未得到充分探索。因此，本研究通过液相色谱/电喷雾串联质谱（LC-ESI/MS/MS）同时测定肺癌患者血清中 Trp 和 Kyn 的浓度，以探讨 IDO 活性与肺癌临床参数的相关性。
采用 LC-ESI/MS/MS 同时测定 123 例肺癌患者和 45 例健康对照者血清中 Trp 和 Kyn 的浓度。通过计算血清 Kyn/Trp 比值（Kyn/Trp 比值）来估计 IDO 活性。
肺癌患者的 Trp 浓度明显低于健康对照组（分别为 62.6+/-15.8μM 与 71.1+/-11.8μM，p=0.0007），而 Kyn 浓度明显高于对照组（分别为 2.82+/-1.17μM 与 2.30+/-0.56μM，p=0.0036）。Kyn/Trp 比值所反映的 IDO 活性在患者中明显高于对照组（分别为 47.1+/-21.3 与 32.9+/-9.10，p<0.0001）。此外，晚期肺癌患者的 Trp 浓度明显低于早期患者，IDO 活性明显高于早期患者（p=0.0058 和 p=0.0209）。
肺癌患者的 IDO 活性增加，并且更高的 IDO 活性与更晚期的疾病阶段相关。这些结果表明，IDO 活性的增加与肺癌的疾病进展有关，可能通过其免疫抑制作用。
