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.
Highlights
Germ cell tumors (GCTs) are the most common cancer disease seen in young men between 20-40 years of age [1]
We sought to define the association between DNA damage levels in peripheral blood lymphocytes (PBLs) of chemotherapy-naïve GCT patients and the patients’ outcome
Patients with high DNA damage levels in PBLs before chemotherapy had significantly worse Progression-free survival (PFS) and Overall survival (OS) compared to patients with low DNA damage levels, as measured by the Comet assay
Summary
Germ cell tumors (GCTs) are the most common cancer disease seen in young men between 20-40 years of age [1]. DNA repair capacity as well as DNA damage levels in tumor cells and/or PBLs may serve as potential predictive biomarkers for better stratification of GCT patients. They may represent new specific targets for therapy of this disease. XPA levels are lower in sensitive GCTs [17], indicating that expression levels of these two key NER factors may potentially be used as prognostic markers and potential biomarkers of CDDP response They could serve as the basis for developing of clinically relevant strategies and therapeutic targets in treatment of GCTs resistant to CDDP [23]
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