EIF2S2 as a Prognostic Marker and Therapeutic Target in Glioblastoma: Insights into its Role and Downstream Mechanisms

Glioblastoma (GBM) the most common and most aggressive primary brain tumor has a five-year survival rate of less than 5%. The onset of GBM is very complicated and has always been the focus of researchers. This study analyzed data from 155 GBM and 5 normal tissues from The Cancer Genome Atlas (TCGA), and patients were categorized into high and low EIF2S2 expression groups. The Overall survival and disease-free survival of GBM patients in low expression of EIF2S2 group were significantly higher than those in high expression of EIF2S2 group (p < 0.001), and the expression level of EIF2S2 was significantly correlated with tumor grade (p < 0.001) and tumor recurrence (p < 0.001). The study designed three different short hairpin RNA (shRNA) sequence vectors, identifying shEIF2S2-1 as the most effective. This vector significantly reduced EIF2S2 expression, cell proliferation, and migration while increasing apoptosis in SHG-44 and U251 cells (p < 0.01). By detecting SHG-44 cells infected with shEIF2S2 vector and shCtrl with human whole gene expression chip, we identified WNT5A that is a downstream target gene of EIF2S2. Interfering with WNT5A and overexpressing EIF2S2 in SHG-44 and U251 cells revealed that EIF2S2 regulates WNT5A expression. This regulation led to an increased apoptosis rate (p < 0.05) and a significant reduction in cell migration (p < 0.05) in both the EIF2S2 overexpression and shWNT5A interference groups, confirming that WNT5A is a downstream regulatory target of EIF2S2. This study revealed the key role of EIF2S2 in GBM and its potential molecular mechanism.