Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer

AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups(r s = 0.494, P = 0.0001 and r s= 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls(controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.

Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma

AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P &#x0003e; 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P &#x0003c; 0.01). Urinary biopterin was significantly higher in cancer cases (P &#x0003c; 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P &#x0003c; 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% &#x000b1; 6.11%) than negative colorectal cancer patients (24.04% &#x000b1; 6.90%), (P &#x0003c; 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P &#x0003c; 0.01 and P &#x0003c; 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.