1243 FOXM1*3 Overexpression Correlates to Staging of Astrocytic Glioma

INTRODUCTION: Diffuse gliomas are a group of primary brain tumors characterized by the presence of neoplastic glial-lineage cells. WHO 2021 classification of gliomas recognizes the mutational status of the isocitrate dehydrogenase-1(IDH-1,G395A) gene and the 1p/19q codeletion as identification of cell lineage and a prognosis marker. Transcription factors are binding proteins of genomic DNA and can activate or suppress gene expression. Forkhead box M1(FOXM1) is a transcription factor for Forkhead box(Fox) proteins, a superfamily which is defined by a conserved winged helix DNA binding domain. FOXM1 is a key regulator of both G1/S and G2/M phases of cell cycle and mitotic spindle integrity, it also plays an important role in angiogenesis, DNA damage repair and tissue regeneration. The human FOXM1 gene consists of 10 exons, two of them alternatively spliced. This splicing gives rise to three isoforms: FOXM1*1,*2 and *3. FOXM1*3 is the smallest isoform and is overexpressed in proliferative tissue such as malignant tumors. METHODS: A control group of 10 brain cortex, 22 A2, 13 O2, 11 A3, 3 O3, 6 A4 and 46 GBM with histological and molecular diagnosis of astrocytoma, oligodendroglioma and glioblastoma from 2011 to 2022 were included. The diagnosis correlated with patient outcome. mRNA FOXM1*3 and its housekeeping gen IPO8 was quantified by qPCR with Taqman probes. Data analysis was conducted by MannWhitney U test. RESULTS: There was a statistically significant difference between expression of mRNA FOXM1*3 in normal brain tissue compared to tumor tissue (p < 0.001). The transcript allowed differentiation between grade 2, 3 and 4 astrocytomas (p < 0.005), nevertheless there was no difference between astrocytic versus oligodendrocytic lineage, and grade 4 astrocytoma versus glioblastoma. CONCLUSIONS: The normalized expression of transcript FOXM1*3 allows differentiation of astrocytic gliomas grades.