The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer
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Zuzana Sestakova1,*, Katarina Kalavska1,2,*, Lenka Hurbanova 1, Dana Jurkovicova1, Jan Gursky1, Michal Chovanec3,4, Daniela Svetlovska2, Vera Miskovska5, Jana Obertova3,4, Patrik Palacka3,4, Katarina Rejlekova3,4, Zuzana Sycova-Mila4, Silvia Cingelova4, Stanislav Spanik5,6, Jozef Mardiak3,4, Miroslav Chovanec1,#, Michal Mego2,3,4,#
1Department of Genetics Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
2Translational Research Unit, Faculty of Medicine, Comenius University, National Cancer Institute, Bratislava, Slovakia
32nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
4Department of Oncology, National Cancer Institute, Bratislava, Slovakia
51st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovakia
6Department 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
Miroslav Chovanec, email: [email protected]
Michal Mego, email: [email protected]
Keywords: DNA damage, DNA repair, cisplatin, germ cell tumors, prognostic marker
Received: July 04, 2016 Accepted: September 29, 2016 Published: October 07, 2016
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.
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