Forkhead Box M1 isoform 3 overexpression is associated with malignancy grade in adult-type diffuse gliomas

Forkhead Box M1 is a transcription factor that is overexpressed in both its mRNA and its protein in various types of cancer. The active Forkhead Box M1 isoform 3 (FOXM1*3) is, moreover, associated with cancer progression. However, little is known about the role of this isoform concerning the degree of malignancy in brain gliomas. This study evaluated the association between overexpression of the FOXM1*3 and the degree of malignancy in adult-type diffuse gliomas (ATDGs).

We conducted a prospective study involving 81 samples from patients with ATDGs and ten samples from healthy control cortices. Quantification of the FOXM1*3 transcript and the housekeeping gene, importin 8 (IPO8), was performed using qPCR with Taqman probes. Tumor samples were classified based on their degree of malignancy and cell lineage. Progression-free survival (PFS) was observed through long-term follow-up. The data were then analyzed using the Kruskal-Wallis, Mann-Whitney U and log-rank (Mantel-Cox) tests.

The most frequent type of cell differentiation was astrocytic, with astrocytomas and glioblastomas accounting for 80.2 % of cases. The primary histopathological-molecular diagnosis group was glioblastoma, at 35.8 %. There was a significant difference in FOXM1*3 expression between the control and glioma groups (p < 0.001). Transcript expression showed significant differences among grade-2, -3, and -4 gliomas (p < 0.005-0.0001). Significant differences were also detected between grade-2 and -3 astrocytomas (p < 0.005) and glioblastomas (p < 0.0001), but not between astrocytomas and oligodendrogliomas of the same grade.

We observed that overexpression of FOXM1*3 can rectify intra-observer discordance in determining the malignancy grade of gliomas, particularly in grade 3. It can be considered a supplementary tool.