The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer

// Zuzana Sestakova 1, * , Katarina Kalavska 1, 2, * , Lenka Hurbanova 1 , Dana Jurkovicova 1 , Jan Gursky 1 , Michal Chovanec 3, 4 , Daniela Svetlovska 2 , Vera Miskovska 5 , Jana Obertova 3, 4 , Patrik Palacka 3, 4 , Katarina Rejlekova 3, 4 , Zuzana Sycova-Mila 4 , Silvia Cingelova 4 , Stanislav Spanik 5, 6 , Jozef Mardiak 3, 4 , Miroslav Chovanec 1, # , Michal Mego 2, 3, 4, # 1 Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia 2 Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia 3 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia 4 Department of Oncology, National Cancer Institute, Bratislava, Slovakia 5 1st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia 6 Department of Oncology, St. Elizabeth Cancer Institute, Bratislava, Slovakia * K-K and Z-S share the first authorship # M-CH and M-M share the last authorship Correspondence to: Miroslav Chovanec, email: miroslav.chovanec@savba.sk Michal Mego, email: misomego@gmail.com Keywords: DNA damage, DNA repair, cisplatin, germ cell tumors, prognostic marker Received: July 04, 2016     Accepted: September 29, 2016     Published: October 07, 2016 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-naive GCT patients. PBLs isolated from 59 chemotherapy-naive 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.