Deciphering the potential influence of BNCT on gene expression in normal cells through bioinformatic analysis of the -particles-induced transcriptome data

Background: Boron Neutron Capture Therapy (BNCT) is a promising radiotherapy option targeted towards treatment-resistant solid tumors, based on the nuclear fission of 10B under neutron irradiation (alpha-particles). However, BNCT may cause damage to normal cells and tissues to a certain extent, and therefore the related mechanism needs to be further explored. This study aims to explore potential risk factors of BNCT on normal cells and tissues based on bioinformatic analysis of alpha-particles radiation-induced transcriptome changes. Methods: Datasets about alpha-particles treated fibroblast (GSE12435 and GSE21059), lymphocyte (GSE80547), skin tissues (GSE23901, GSE23903, GSE23899, GSE23899 and GSE32541), were downloaded from the Gene Expression Omnibus database. Transcriptome analyses were conducted, including GO functional annotation, KEGG pathway enrichment analysis, PPI network, and correlation analysis of transcription factors. Results: KEGG enrichment analysis revealed that the P53 signaling pathway was significantly enriched in fibroblasts and lymphocytes treated with alpha-particles irradiation. The core genes associated with irradiation exposure in these cells included CDKN1A, MDM2, DDB2, GADD45A, and FDXR. In skin tissue, hub-genes closely related to inflammation and tissue damage were observed in both the indirectly irradiated group (CXCL8, IL2, MMP9, CXCR4, and CCL5) and the directly irradiated group (IL1B, EGF, IL2, TLR4, and MMP9). Conclusions: In response to alpha-particles exposure, key signaling pathways such as the P53 pathways and signature genes like CDKN1A are involved. These discoveries are crucial for comprehending the possible effects of BNCT and offer significant resources and information to minimize the negative impacts of BNCT on non-tumorous tissues.