Low-dose ionising radiation from cardiac catheterisation alters blood microRNA profiles in pediatric patients targeting key cancer pathways

Background The risk of cancer from medical exposure to ionizing radiation in pediatric patients, particularly those with congenital heart disease (CHD), is a significant concern due to the need for repeated procedures throughout their lifetime. To better assess cancer risks associated with low-dose radiation exposure, it is essential to understand how such exposure induces cellular and molecular damage. Purpose This study aimed to examine the dynamic expression profile of miRNAs in blood samples from CHD patients following cardiac catheterization (CC) Methods We conducted small RNA sequencing in a discovery cohort of 10 CAD patients at three time points: immediately before (T0), immediately after surgery (T1), and approximately one year post-cardiac catheterization (T2). The findings were further validated using qRT-PCR in a separate cohort of 15 CAD patients. To explore pathway enrichment, we utilized the DIANA tool miRPath v.4, which simultaneously analyzes the combinatorial effects of differentially expressed miRNAs based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) annotations Results At the discovery stage, DESeq2 identified 74 miRNAs that were significantly differentially expressed between the T1 and T0 groups, 69 between the T2 and T0 groups, and 41 between the T2 and T1 groups (q-value < 0.05 and |log2(fold change)| >1). Among these, 16 miRNAs (9 upregulated and 7 downregulated) were found to be consistently dysregulated in both T1 and T2 compared to T0. Functional enrichment analysis revealed that cancer-related pathways had the strongest significant association with the combinatorial effect of differentially expressed miRNAs in both T1 and T2 (q-value = 0.000001). The confirmation of three commonly dysregulated miRNAs—hsa-miR-125a-3p, hsa-miR-760, and hsa-miR-144-3p—in both T1 and T2 compared to T0 via qRT-PCR was consistent with the RNA sequencing results Conclusions Radiation exposure from pediatric CC procedures leads to specific dysregulation of blood miRNAs, which are involved in signaling pathways associated with cancer.