Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer.
BACKGROUND
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.


METHODS
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+/-15.8microM 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).


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.
Suzuki
Yuzo
Y
Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Hanadayama Higashiku, Hamamatsu, Shizuoka 431-3125, Japan.
Suda
Takafumi
T
Furuhashi
Kazuki
K
Suzuki
Masako
M
Fujie
Michio
M
Hahimoto
Dai
D
Nakamura
Yutaro
Y
Inui
Naoki
N
Nakamura
Hirotoshi
H
Chida
Kingo
K
D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood* / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014364:Tryptophan / Q000097:blood* / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan