ABSTRACT
Peripheral blood mononuclear cells (PBMC) represent an easily available population of cells for the studies on remote effects of lung cancer. NADH dehydrogenase (ubiquinone) Fe-S protein-1 (Ndufs1), a marker of mitochondrial complex I, and mitochondrially encoded cytochrome c oxidase 1 (MTCO1), a marker of complex IV, may participate in cognitive decline during the course of lung cancer. In this study, Ndufs1 and MTCO1 expression in PBMC was evaluated by means of ELISA in 80 lung cancer patients. Mini-Mental State Examination (MMSE) were conducted Trail Making Tests (TMT-A and TMT-B) at baseline and after the 6 months' follow-up. Autoantibodies were identified by means of indirect immunofluorescence and line blot. We found that enhanced levels of Ndufs1 in PBMC were related to impaired cognitive performance; TMT-A of 13.6 ± 3.1 s and TMT-B of 162.5 ± 46.4 s compared with 8.6 ± 4.5 s (p = 0.003) and 124.8 ± 51.8 s (p < 0.05), respectively, in the case of low Ndufs-1 levels. The Ndufs1 expression at baseline was associated with MMSE - τb (Kendall's tau-b) = -0.31; p = 0.024; TMT-A - τb = 0.30; p = 0.001), and TMT-B - τb = 0.199; p = 0.012) after the 6 months' follow-up. Higher MTCO1 expression was accompanied by worse TMT-A results than in case of inhibited MTCO1; 11.1 ± 5.8 s vs. 8.5 ± 4.1 s; respectively; p = 0.048. MTCO1 expression was correlated with TMT-A results (τb = 0.17; p = 0.034) at baseline. We conclude that stimulation of PBMC mitochondrial function in lung cancer patients is associated with cognitive impairment. Mitochondrial dysfunction in PBMC may reflect cytotoxicity responsible for neurological deficits.
Subject(s)
Biomarkers, Tumor/blood , Cognition Disorders/diagnosis , Electron Transport Complex IV/blood , Lung Neoplasms/complications , NADH Dehydrogenase/blood , Adenocarcinoma/complications , Adenocarcinoma/pathology , Adenocarcinoma/psychology , Carcinoma, Large Cell/complications , Carcinoma, Large Cell/pathology , Carcinoma, Large Cell/psychology , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/psychology , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/psychology , Cognition Disorders/blood , Cognition Disorders/etiology , Cognition Disorders/psychology , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Leukocytes, Mononuclear/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/psychology , Male , Middle Aged , Neoplasm Staging , Neuropsychological Tests , Prognosis , Psychomotor Performance , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/psychology , Trail Making TestABSTRACT
Cognitive impairment develops as a clinical manifestation of immune-mediated indirect effects of malignancy in lung cancer patients. This study aimed to evaluate the effects of humoral immune response on cognition in lung cancer patients. Fifty-one lung cancer patients were subjected to neurological examination: Mini Mental State Examination (MMSE), Trail Making Test (TMT), and Hamilton scale. The Psychology Experiment Building Language software was used for the evaluation of digit span, simple reaction time (SRT), and choice reaction time (CRT) tests. Serum samples were tested for the presence of onconeuronal antibodies and antineural antibodies. The results demonstrate that autoantibodies were found in 31 % patients. MMSE scores were lower (26.7 ± 2.7) in seropositive patients than in seronegative subjects (28.7 ± 1.2; p = 0.013). Executive functions were also influenced by the presence of autoantibodies. The humoral immune response in lung cancer patients affected both SRT and CRT. We conclude that the humoral immune response in lung cancer patients is associated with cognitive impairment. Cognitive impairment is associated with both specific reactions against onconeuronal or antineural antigens and non-organ specific reactions against nucleosome antigens.
