Mitochondrial subtype MB-G3 contains potential novel biomarkers and therapeutic targets associated with prognosis of medulloblastoma.

Abstract

Background: Medulloblastoma is the most common malignant brain tumor in children. There are four groups, each with different causal mutations, affected pathways and prognosis. Here, we investigated the role of mitochondria in medulloblastoma and whether there are differences between the different groups.

Methods: We compared the gene expression levels in the four different medulloblastoma groups (MB-WNT, MB-SHH, MB-G3 and MB-G4), with the focus on genes associated with mitochondria. We used several tools including Salmon, Tximeta, DESeq2, BiomaRt, STRING, Ggplot2, EnhancedVolcano, Venny 2.1 and Metscape.

Results: A total of 668 genes were differentially expressed and the most abundant genes were associated with cell division pathway followed by modulation of chemical synaptic transmission. We also identified several genes (ABAT, SOX9, ALDH5A, FOXM1, ABL1, NHLH1, NEUROD1 and NEUROD2) known to play vital role in medulloblastoma. Comparative expression analysis revealed OXPHOS complex-associated proteins of mitochondria. The most significantly expressed genes in the MB-SHH and MB-G4 groups were AHCYL1 and SFXN5 while PAICS was significantly upregulated in MB-WNT group. Notably, MB-G3 contained the most downregulated genes from the OXPHOS complexes, except COX6B2 which was strongly upregulated.

Conclusions: We show the importance of mitochondria and compare their role in the four different medulloblastoma groups.