Investigating Molecular Determinants of Cancer Cell Resistance to Ionizing Radiation Through an Integrative Bioinformatics Approach

Halil Ibrahim Toy; Gökhan Karakülah; Panagiota I Kontou; Hani Alotaibi; Alexandros G Georgakilas; Athanasia Pavlopoulou

doi:10.3389/fcell.2021.620248

Investigating Molecular Determinants of Cancer Cell Resistance to Ionizing Radiation Through an Integrative Bioinformatics Approach

Front Cell Dev Biol. 2021 Apr 7:9:620248. doi: 10.3389/fcell.2021.620248. eCollection 2021.

Authors

Halil Ibrahim Toy^{1

2}, Gökhan Karakülah^{1

2}, Panagiota I Kontou³, Hani Alotaibi^{1

2}, Alexandros G Georgakilas⁴, Athanasia Pavlopoulou^{1

2}

Affiliations

¹ Izmir Biomedicine and Genome Center, Izmir, Turkey.
² Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey.
³ Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece.
⁴ DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou, National Technical University of Athens, Athens, Greece.

Abstract

Eradication of cancer cells through exposure to high doses of ionizing radiation (IR) is a widely used therapeutic strategy in the clinical setting. However, in many cases, cancer cells can develop remarkable resistance to radiation. Radioresistance represents a prominent obstacle in the effective treatment of cancer. Therefore, elucidation of the molecular mechanisms and pathways related to radioresistance in cancer cells is of paramount importance. In the present study, an integrative bioinformatics approach was applied to three publicly available RNA sequencing and microarray transcriptome datasets of human cancer cells of different tissue origins treated with ionizing radiation. These data were investigated in order to identify genes with a significantly altered expression between radioresistant and corresponding radiosensitive cancer cells. Through rigorous statistical and biological analyses, 36 genes were identified as potential biomarkers of radioresistance. These genes, which are primarily implicated in DNA damage repair, oxidative stress, cell pro-survival, and apoptotic pathways, could serve as potential diagnostic/prognostic markers cancer cell resistance to radiation treatment, as well as for therapy outcome and cancer patient survival. In addition, our findings could be potentially utilized in the laboratory and clinical setting for enhancing cancer cell susceptibility to radiation therapy protocols.

Keywords: DNA damage repair; bioinformatics; biomarkers; cancer cell radioresistance; gene expression profiles; ionizing radiation.