Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to the toxic effects of CDDP-based chemotherapy. Previously, in a pilot study, we observed prognostic value of the DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. This study was aimed to validate the prognostic value of the DNA damage level in PBL in chemo-naïve, as well as chemotherapy pre-treated GCT patients.
PBLs isolated from 123 GCT patients (101 chemotherapy-naïve and 22 chemotherapy pre-treated) baseline and before 2nd cycle of chemotherapy were included into this prospective study. The DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage of DNA in tail by the Metafer-MetaCyte analyzing software. The DNA damage level in PBL was categorized as ‘low’ or ‘high’ according to the cut-off level of the mean.
The mean ± SEM (standard error of the mean) of the endogenous DNA damage level was 5.25 ± 0.64. Chemotherapy-naïve patients with “low” DNA damage levels at baseline had significantly better progression-free survival (PFS) (hazard ratio [HR] = 0.05 95%CI (0.02 – 0.17), P = 0.0001) and overall survival (OS) (HR = 0.00, P = 0.0002, no death occurred in patients with “low” DNA damage level) compared to patients with “high” DNA damage levels. In multivariate analysis, prognostic value of the DNA damage level in PBL was significantly associated with PFS and OS independently of IGCCCG risk group. Moreover, there was significant correlation between the DNA damage level and response to treatment, non-pulmonary visceral metastases, number of metastatic sites, presence of mediastinal lymph nodes metastases and serum tumor markers level. There was no prognostic value of DNA damage level in PBL before 2nd cycle of chemotherapy and/or in pre-treated GCTs.
These data suggest that the DNA damage levels in PBLs of GCT patients are a novel prognostic marker timely identifying patients with poor outcome. We hypothesize that altered DNA damage level in PBLs could be induced by GCTs similarly to cancer-related immunosuppression and is abolished by administration of chemotherapy.
Clinical trial identification
Legal entity responsible for the study
VEGA 1/0043/18, APVV-15-0086.
All authors have declared no conflicts of interest.