Emerging molecular networks common in ionizing radiation, immune and inflammatory responses by employing bioinformatics approaches

Abstract

Efficient radiation therapy is characterized by enhanced tumor cell killing involving the activation of the immune system (tumor immunogenicity) but at the same time minimizing chronic inflammation and radiation adverse effects in healthy tissue. The aim of this study was to identify gene products involved in immune and inflammatory responses upon exposure to ionizing radiation by using various bioinformatic tools. Ionizing radiation is known to elicit different effects at the level of cells and organism i.e. DNA Damage Response (DDR), DNA repair, apoptosis and, most importantly, systemic effects through the instigation of inflammatory 'danger' signals and innate immune response activation. Genes implicated both in radiation and immune/inflammatory responses were collected manually from the scientific literature with a combination of relevant keywords. The experimentally validated and literature-based results were inspected, and genes involved in radiation, immune and inflammatory response were pooled. This kind of analysis was performed for the first time, for both healthy and tumor tissues. In this way, a set of 24 genes common in all three different phenomena was identified. These genes were found to form a highly connected network. Useful conclusions are drawn regarding the potential application of these genes as markers of response to radiation for both healthy and tumor tissues through the modulation of immune and/or inflammatory mechanisms.

Keywords: Bioinformatics; Biomarkers; Immune response; Inflammatory response; Ionizing radiation; Pathways.