title: The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer.
abstract: Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 - 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 - 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome.
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sestakova
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.|Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kalavska
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Hurbanova
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Dana
authors.initials: D
authors.lastname: Jurkovicova
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Gursky
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Chovanec
authors.affiliation: Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Svetlovska
authors.affiliation: 1st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia.
authors.forename: Vera
authors.initials: V
authors.lastname: Miskovska
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Jana
authors.initials: J
authors.lastname: Obertova
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Patrik
authors.initials: P
authors.lastname: Palacka
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Rejlekova
authors.affiliation: Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sycova-Mila
authors.affiliation: Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cingelova
authors.affiliation: 1st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia.|Department of Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovakia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Spanik
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Mardiak
authors.affiliation: Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Chovanec
authors.affiliation: Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia.|2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.|Department of Oncology, National Cancer Institute, Bratislava, Slovakia.
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
keywords: DNA damage; DNA repair; cisplatin; germ cell tumors; prognostic marker