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J. Gazdulska
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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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P1.04-054 - Mitochondrial Status in Peripheral Blood Mononuclear Cells in Relation to Cognitive Impairment in Lung Cancer Patients (ID 1435)
09:30 - 09:30 | Author(s): J. Gazdulska
- Abstract
Background:
Mitochondrial dysfunction is observed not only in lung cancer cel, but can develop in peripheral tissues. Peripheral blood mononuclear cells (PBMC) represent an available population of cells that can be used for the studies on remote effects of lung cancer. NADH dehydrogenase (ubiquinone) Fe-S protein 1 (Ndufs1) is located at the inner mitochondrial and transfers electrons from NADH to the respiratory system. Mitochondrially encoded cytochrome c oxidase I (MT-CO1) is involved in the coupling between O2 reduction and proton pumping. The changes in both key components of respiratory system reflect mitochodrial status. On the other hand the impairment of mitochondrial function may be crucial among pathomechanisms leading to neurological deficits. The aim of the study was evaluate mitochondrial status in PBMC in relation to the cognition in lung cancer patients.
Methods:
The study included 80 (24 females and 56 males, aged 61.5±6.7 years) consecutive lung cancer patients (5 small-cell lung cancer, 75 non-small cell lung cancer) 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 Ndufs1 a marker of mitochondrial complex I and MTCO1 a marker of complex IV in PBMC was evaluated by means of ELISA and expressed in pg per mg of protein. 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.. Patients serum was tested for the presence of onconeuronal antibodies with indirect immunofluorescence as a screening and Line blot as confirmation test.
Results:
Ndufs 1 expression in PBMC was lower in patient with peripheral nervous system involvement (0.00; 0.0-3.6218 ; median; minimum-maximum) than in subjects without neurological deficit (0.0; 0.0-8.61; median; minimum-maximum; P= 0,024). Up-regulated expression of Ndufs 1 in PBMC is associated with worse TMT- A (13.61±3.13s) than in patients with down-regulated complex I marker (8.60±4.51s; P=0.003). Similarly TMT- B results were worse in patients with higher Ndufs 1 expression (162.48±46.40s) than in cases with inhibited Ndufs1 (124.78±51.77s; P<0,05). Ndufs1 expression correlated negatively with MMSE 6 months after lung cancer diagnosis (Kendall tau =-0.310; P=0.0236), and positively with Hamilton scale score after 6 months (Kendall tau=0.288; P=0.0428), TMT-A (Kendall tau=0.301; P=0.0001) and TMT-B (Kendall tau=0.199; P=0.0120) at baseline. Up-regulated expression of MTCO1 was associated with worse TMT-A results (11.05±5.81s) compared to down-regulated marker of mitochondrial complex IV (8.52±4.14s; P=0.048). MTCO1 expression correlated positively with TMT-A results (Kendall tau=0.167; P=0.0344) at baseline. In 12 patients onconeuronal antibodies were identified (Ma/Ta, Yo, Ri). No differences in Ndufs1 and MTCO1 expression were found between patients with onconeronal antibodies and seronegative subjects.
Conclusion:
Up-regulation of mitochondrial complex I and IV in PBMC of lung cancer patients is associated with cognitive decline. Stimulation of mitochondria status in PBMC may indicate cytotoxic response leading to cognitive impairement.
