Cognitive impairment and biomarkers of gut microbial translocation in testicular germ cell tumor survivors.

Autor:	Chovanec M; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Kalavska K; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia., Obertova J; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Palacka P; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Rejlekova K; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Sycova-Mila Z; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Orszaghova Z; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Lesko P; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., De Angelis V; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Vasilkova L; Department of Psychology, Faculty of Philosophy, Comenius University, Bratislava, Slovakia., Svetlovska D; Department of Clinical Trials, National Cancer Institute, Bratislava, Slovakia., Mladosievicova B; Institute of Pathological Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Mardiak J; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia., Pastorek M; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Vlkova B; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Celec P; Institute of Pathological Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia., Mego M; 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.; Department of Medical Oncology, National Cancer Institute, Bratislava, Slovakia.; Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Mar 21; Vol. 13, pp. 1146032. Date of Electronic Publication: 2023 Mar 21 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1146032
Abstrakt:	Background: Survivors of testicular germ cell tumors (GCT) may suffer from late cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis. Methods: GCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial translocation and dysbiosis high mobility group box-1 (HMGB-1), lipopolysaccharide, d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6). Results: GCT survivors with higher sCD14 (above median) had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overall cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and lipopolysaccharide. Survivors treated with ≥ 400mg/m2 vs < 400mg/m2 of cisplatin-based chemotherapy had a higher lipopolysaccharide (567.8 μg/L ± 42.7 vs 462.9 μg/L ± 51.9, (p = 0.03). Conclusions: sCD14 is a marker of monocytic activation by lipopolysaccharide and may also serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors within the gut-brain axis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Chovanec, Kalavska, Obertova, Palacka, Rejlekova, Sycova-Mila, Orszaghova, Lesko, De Angelis, Vasilkova, Svetlovska, Mladosievicova, Mardiak, Pastorek, Vlkova, Celec and Mego.)
Databáze:	MEDLINE
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