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I. Golda-Gocka
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-075 - Kynurenine Pathway Activity in Peripheral Blood Mononuclear Cells and Cognitive Functions in Lung Cancer Patients (ID 1440)
09:30 - 17:00 | Author(s): I. Golda-Gocka
- Abstract
Background:
The kynurenine pathway is crucial for tryptophan metabolism, which has been shown to be active both in macrophages and microglial cells. L-Kynurenine (L-KYN) is transported across the blood-brain barrier and serves as a source for the synthesis of all the other metabolites of the kynurenine pathway. Glial cells have the enzymatic capability for the biosynthesis of brain kynurenines as kynurenine aminotransferase (KAT). KAT converts L-KYN to kynurenic acid, which is an inhibitor of glutamate neurotransmission. The lowered KAT activity was observed in the plasma and brains of patients with neurodegenerative disorders followed by a tendency to a decrease KYNA in plasma and brains. Peripheral blood mononuclear cells (PBMC) can be considered as representative for metabolic changes in peripheral tisues during the course of lung cancer. With this background in mind we have undertaken the evaluation of translocator protein 18 kDa (TSPO), which reflects microglia activation, G Protein-coupled Receptor (GPR35), a KYNA receptor and kynurenine aminotransferase II (KAT) in PBMC and serum L-KYN concentration in relations to cognitive functions in lung cancer patients.
Methods:
We included in the study 80 consecutive lung cancer patients (5 small-cell lung cancer, 75 non-small cel lung cancer, 24 females and 56 males, aged 61.5±6.7 years) hospitalized in Clinical Oncology with The Sub-department of Diurnal Chemotherapy Wielkopolska Center of Pulmonology and Thoracosurgery of Eugenia and Janusz Zeyland and Chair and Clinic of Oncology. PBMC were isolated by density gradient centrifugation. The expression of TSPO, GPR35 KAT in PBMC was evaluated with ELISA. Serum L-KYN concentration was measured by means of spectrofotometric method. Neurological examination, MiniMental State Examination (MMSE), Trail Making Test (TMT) A and B, and Hamilton scale were performed at baseline (time of lung cancer diagnosis) and after 6 months.
Results:
Decreased TSPO expression in PBMC was associated with better results of MMSE evaluation (29.00; 28.0–29.0; median, interquartile range) than in lung cancer patients with up-regulated TPSO (28.0; 26.0–28.7; P=0.016). Also, TMT-A results were better in lung cancer patients with down-regulated TPSO (8.41±3.68s) compared to the subject with stimulated TPSO (12.92±7.30s; P=0.002). TSPO expression in PBMC negatively correlated with MMSE score (Kendall’s tau = -0.182; P=0.0178) and positively with TMT-A (Kendall’s tau = 0.168; P=0.0309) evaluated at baseline. The up-regulation of KAT expression in PBMC was associated with better cognitive functions measured with MMSE 6 months after baseline (28.4±0.7) comparing to lung cancer patients with inhibited KAT (27.1±1.8). KAT correlated positively with MMSE scoring 6 months after baseline (Kendall’s tau= 0.308; P=0.0234).The expression of GPR35 in PBMC did not correlated with cognitive measures. Serum L-KYN concentration correlated negatively with TMT-A evaluated 6 months after baseline (Kendall’s tau= -0.586; P=0.0141). Moreover, TPSO expression correlated positively with KAT (Kendall’s tau= 0.253, P=0.0009) and negatively with GPR35 (Kendall’s tau= -0.173, P=0.0491), but no correlation with L-KYN was found.
Conclusion:
Stimulation of kynurenine pathway in PBMC seems to be protective against cognitive decline during the course of lung cancer. Microglial activation can be independent pathomechanism leading to cognitive impairement in lung cancer patients.
