Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in the Lung Adenocarcinoma: in Vitro and Bioinformatic Studies

Objective: ionizing radiation (ir) is one of the major therapeutic approaches in the non-small cell lung cancer (nsclc); however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition (emt) and the cancer stem cell phenotype. therefore, we aimed to determine whether ir promote emt/csc and to investigate the clinical relevance of emt/csc hallmark genes. materials and methods: in this experimental and bioinformatic study, a549 cell line was irradiated with a high dosage (6 gy) or a fractionated regimen (2 gy/day for 15 fractions). the emt-related features, including cellular morphology, migratory and invasive capacities were evaluated using scratch assay and transwell migration/invasion assays. the mrna levels of emt-related genes (cdh1, cdh2, snai1 and twist1), stemness-related markers (cd44, prom1, and aldh1a1) and the cdh2/cdh1 ratio were evaluated via real-time polymerase chain reaction (pcr). the clinical significance of these genes was assessed in the lung adenocarcinoma (luad) samples using online databases. results: irradiation resulted in a dramatic elongation of cell shape and enhanced invasion and migration capabilities. these emt-like alterations were accompanied with enhanced levels of snai1, cdh2, twist1, cd44, prom1, and aldh1a1 as well as an enhanced cdh2/cdh1 ratio. tcga analysis revealed that, twist1, cdh1, prom1 and cdh2 were upregulated; whereas, cd44, snai1 and aldh1a1 were downregulated. additionally, correlations between snai1-twist1, cdh2- twist1, cdh2-snai1, and aldh1a1-prom1 was positive. kaplan-meier survival analysis identified lower expression of cdh1, prom1 and aldh1a1 and increased expression of cdh2, snai1, and twist1 as well as cdh2/cdh1 ratio predict overall survival. additionally, downregulation of aldh1a1 and upregulation of cdh2, snai1 and twist1 could predict a shorter first progression. conclusion: altogether, these findings demonstrated that ir promotes emt phenotype and stem cell markers in a549 cell line and these genes could function as diagnostic or prognostic indicators in luad samples