Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)

Abstract

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

Machine learning on genome-wide association studies to predict the risk of radiation-associated contralateral breast cancer in the WECARE Study

“…The most significant GO term in the analysis, cAMP-mediated signaling, has been shown to promote radiationinduced apoptosis in human lung cancer cells via interaction with the ATM gene [63]. The regulation of response to wounding has been previously identified by the transcriptome experiment by Yeles, et al [64] as a significantly enriched process in bystander cells adjacent to the region irradiated with alpha particles.…”

Machine Learning Methods to Identify Genetic Correlates of Radiation-Associated Contralateral Breast Cancer in the WECARE Study

“…The most significant GO term in the analysis, cAMP-mediated signaling, has been shown to promote radiation-induced apoptosis in human lung cancer cells via interaction with the ATM gene 42 . The regulation of response to wounding has been previously identified by the transcriptome experiment as a significantly enriched process in bystander cells adjacent to the region irradiated with alpha particles 43 .…”

Changes in gene expression as one of the key mechanisms involved in radiation‑induced bystander effect (Review)

“…However, in certain cases, the lack of transcriptional responses may not be associated with the RIBE. The most reports indicate that the transcriptional mechanisms underlying the RIBE following α-particle and 12 C IR exposures may differ substantially; however, a 28-gene RIBE signature may be a common theme among these exposures ( 82 ). The differences and similarities across gene expression changes in the context of the RIBE are presenting in Table I , which summarizes these transcriptional responses as reported in the published literature.…”