PATH-16. The Prognostic Significance of ALKBH4 Expression in Glioblastoma Patients

Abstract BACKGROUND Gene methylation is closely related to epigenetics, influencing both homeostasis formation and maintenance as well as carcinogenesis. ALKBH4, a member of the AlkB homolog (ALKBH) family, regulates DNA and RNA demethylation. Recent studies have revealed that ALKBH4 is closely associated with the development of various tumors, but its role in glioblastoma remains unclear. METHODS This study first analyzed data from the TCGA and CGGA databases,then we included 98 glioblastoma patients from our hospital. Immunohistochemistry was used to assess ALKBH4 expression, analyzing its correlation with clinicopathological factors and prognosis. RNA-seq analysis was performed on samples from three patients, along with validation through Western blotting (WB) and mRNA assays. RESULTS Analysis of TCGA and CGGA databases revealed that glioblastoma patients with high ALKBH4 expression had poorer clinical outcomes compared to those with low expression. The proportion of cancer cells expressing ALKBH4 was significantly higher in glioblastoma (GBM) compared to other tumor types. In 98 glioblastoma samples, ALKBH4 was found to be expressed not only on the cell membrane but also in the cytoplasm of cancer cells. In the high ALKBH4 expression group, both progression-free survival and overall survival were lower than in the low-expression group. Univariate and multivariate regression analyses indicated that ALKBH4 expression is an independent prognostic factor. RNA-seq showed significant alterations in the PI3K, MAPK, mTOR, cell cycle processes, and epithelial-mesenchymal transition pathways. CONCLUSION ALKBH4 may serve as an important prognostic marker in glioblastoma patients.ALKBH4 makes the prediction of overall survival of GBM patients more accurate and also puts forward a new direction for GBM treatment.