COMPARATIVE ANALYSIS OF RADIATION-INDUCED GENETIC ALTERATIONS AND CANCER-ASSOCIATED MOLECULAR SIGNATURES

Abstract

Ionizing radiation is a potent environmental carcinogen capable of inducing complex DNA damage and long-term genomic instability. While radiation-associated mutational signatures have been well characterized at the genomic level, less is known about how radiation-induced damage intersects with transcriptional regulation across diverse cancer types. Advances in sequencing technologies now enable integrated, multi-layered analyses of radiation-exposed tissues and tumors at the genomic, transcriptomic, and proteomic levels. Such integrative approaches allow not only the identification of structural and sequence-level alterations but also the functional consequences of these changes in terms of gene expression and protein activity. By comparing irradiated tissues, tumor samples, and matched normal controls, it becomes possible to identify shared and distinct molecular signatures that reflect both exposure history and disease state. In this study, we performed a comparative transcriptomic analysis to investigate whether ionizing radiation induces gene expression alterations that overlap with transcriptional changes characteristic of diverse cancer forms. By analyzing four malignancies obtained from Gene Expression Omnibus (GEO) databases, and comparing them with irradiation-responsive genes identified in our previous bioinformatic mouse model investigations, we examined not only disease-specific dysregulation but also non-specific, systemic genetic consequences of radiation exposure. By progressively narrowing the gene spectrum using multilevel filtering, first by expression magnitude, then by Differentially Express Genes (DEG) validation against healthy tissue, and finally by cross-dataset intersections, we identified a narrowed set of genes that are altered both by radiation and across several cancer types. Our findings demonstrate extensive overlap between radiation-responsive genes and genes dysregulated in multiple cancers, suggesting that conserved transcriptional stress responses may contribute to tumorigenesis. This integrative approach provides insight into shared molecular pathways linking radiation exposure and cancer development and supports the identification of candidate biomarkers relevant to radiation-associated malignancies.