DNA damage levels in peripheral blood mononuclear cells before and after first cycle of chemotherapy have comparable prognostic values in germ cell tumor patients

Danica Ivovič; Zuzana Šestáková; Jan Roška; Katarína Kálavská; Lenka Hurbanová; Andrea Holíčková; Božena Smolková; Pavlína Kabelíková; Věra Novotná; Michal Chovanec; Patrik Palacka; Michal Mego; Dana Jurkovičová; Miroslav Chovanec

doi:10.3389/fonc.2024.1360678

DNA damage levels in peripheral blood mononuclear cells before and after first cycle of chemotherapy have comparable prognostic values in germ cell tumor patients

Front Oncol. 2024 Mar 1:14:1360678. doi: 10.3389/fonc.2024.1360678. eCollection 2024.

Authors

Affiliations

¹ Department of Genetics, Cancer Research Institute, Biomedical Research Center, Bratislava, Slovakia.
² Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center, Bratislava, Slovakia.
³ 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.
⁴ 1st Department of Oncology, St. Elisabeth Cancer Institute, Bratislava, Slovakia.

Abstract

Background: Germ cell tumors (GCTs) represent the most frequent solid malignancy in young men. This malignancy is highly curable by cisplatin (CDDP)-based chemotherapy. However, there is a proportion of patients having a poor prognosis due to refractory disease or its relapse. No reliable biomarkers being able to timely and accurately stratify poor prognosis GCT patients are currently available. Previously, we have shown that chemotherapy-naïve GCT patients with higher DNA damage levels in peripheral blood mononuclear cells (PBMCs) have significantly worse prognosis compared to patients with lower DNA damage levels.

Methods: DNA damage levels in PBMCs of both chemotherapy-naïve and first cycle chemotherapy-treated GCT patients have been assessed by standard alkaline comet assay and its styrene oxide (SO)-modified version. These levels were correlated with clinico-pathological characteristics.

Results: We re-confirm prognostic value of DNA damage level in chemotherapy-naïve GCT patients and reveal that this prognosticator is equally effective in GCT patients after first cycle of CDDP-based chemotherapy. Furthermore, we demonstrate that SO-modified comet assay is comparably sensitive as standard alkaline comet assay in case of patients who underwent first cycle of CDDP-based chemotherapy, although it appears more suitable to detect DNA cross-links.

Conclusion: We propose that DNA damage levels in PBMCs before and after first cycle of CCDP-based chemotherapy are comparable independent prognosticators for progression-free and overall survivals in GCT patients. Therefore, their clinical use is highly advised to stratify GCT patients to identify those who are most at risk of developing disease recurrence or relapse, allowing tailoring therapeutic interventions to poor prognosis individuals, and optimizing their care management and treatment regimen.

Keywords: DNA damage level; IGCCCG risk groups; chemotherapy; comet assay; germ cell tumors; peripheral blood mononuclear cells; prognosis; survival.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the VEGA Grant Agency of the Slovak Republic (grant No. 2/0075/23), the Slovak Research and Development Agency (grant no. APVV-17-0384 and APVV-19-0286) and the Integrated Infrastructure Operational Program for the projects “Systemic public research infrastructurebiobank for cancer and rare diseases” (ITMS: 313011AFG5) co-financed by the European Regional Development Fund.