The prognostic significance of MYBL1 and MYBL2 genes in low-grade glioma.

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Background: Low-grade gliomas (LGG) demonstrate heterogeneous clinical behavior despite shared histologic classification. Identifying transcriptional regulators associated with tumor aggressiveness may improve prognostic stratification. MYBL1 and MYBL2 are cell cycle–associated transcription factors implicated in oncogenesis, but their prognostic significance in LGG remains unclear. Methods: RNA sequencing and clinical data from 516 patients in the TCGA-LGG cohort were analyzed. MYBL1 and MYBL2 expression (log2[TPM+1]) were compared across astrocytoma (n=98), oligoastrocytoma (n=76), oligodendroglioma (n=116), and normal brain tissue (n=207). Overall survival (OS) was assessed using Kaplan Meier analysis and multivariate cox proportional hazards models adjusted for histology, grade, age at diagnosis, and IDH status. Gene set enrichment analysis (GSEA) was performed using Reactome, KEGG, MSigDB Hallmark, and GO databases. R v4.3.3 was used for all analyses. Results: Both MYBL1 and MYBL2 were significantly upregulated in LGG compared with normal tissue (MYBL1: log2 fold change [log2FC] =0.710, FDR < 0.001; MYBL2: log2FC=1.379, FDR < 0.001). High MYBL1 expression was associated with inferior OS in the overall LGG cohort (HR=2.2; p=0.0014) and in astrocytoma (HR=3.4; p= 0.0017), but not in oligoastrocytoma (HR=2.2; p=0.13) or oligodendroglioma (HR=1.6; p=0.27). Similarly, elevated MYBL2 expression correlated with worse OS in the overall cohort (HR=2.1; p=0.005) and astrocytoma (HR=2.6; p=0.015), while no significant association was observed in oligoastrocytoma (HR=2.3; p=0.12) or oligodendroglioma (HR=1.3; p=0.6). In multivariate analysis, MYBL1 remained independently associated with poorer OS (HR=1.28, 95% CI 1.04–1.60, p=0.021), whereas MYBL2 did not retain independent prognostic significance. GSEA demonstrated significant enrichment of cell cycle progression, E2F targets, epithelial mesenchymal transition, DNA replication, and mitotic spindle pathways in tumors with high MYBL1/2 expression. Conclusions: MYBL1 and MYBL2 overexpression identify a proliferative subset of low-grade gliomas with poorer outcomes, especially in astrocytoma. Although both associate with aggressive transcriptional programs and reduced survival, only MYBL1 remains an independent prognostic factor after clinicomolecular adjustment, supporting its role as a potential prognostic biomarker.