470P - Mitochondrial ribosomal proteins (MRPs) in glioblastoma multiforme: Omics approach

Background

Glioblastoma multiforme (GBM) is the most common malignant brain tumor. MRPs are involved in mitochondrial translation, with previously revealed role in cancer. Here we aimed to understand their role in GBM.

Methods

Differentially expressed genes (DEGs) were identified through the ‘DESeq2' on R and GEO2R. Survival analysis with optimal expression cutoff for Overall Survival (OS) and median cutoffs for Disease-Free Survival (DFS) based on TCGA-GBM was done using the ‘survival' and 'survminer' R packages, and GEPIA2 online tool. Gene Set Enrichment Analysis (GSEA) was performed using Enrichr tool. miRNA-mRNA networks were constructed using MultiMiR and CytoScape. Immune and methylation analyses were conducted using TIMER2.0 (XCELL) and cBioPortal.

Results

OS estimates indicated worse survival in patients with higher expression of selected MRPs (Table). Further analysis indicated that elevated expression of MRPS33 and MRPL23 is correlated with decreased DFS, with Hazard Ratios (HRs) of 1.80 (p = 0.0012) and 1.70 (p = 0.0039), respectively. GSEA on upregulated genes in high MRPS33-expressers revealed relations to PDGF, NCAM1 interactions, EMT, and integrins in angiognesis. miRNA-mRNA network has identified hub miRNAs, like hsa-miR-1-3p, to have validated interactions with MRPs of interest. Expression of MRPL41, MRPL35, and MRPS33, had negative correlations with HM27/HM450 methylation (Spearman's rho = -0.41, -0.20, and -0.19, respectively; p < 0.05). Finally, there was a positive correlation between MRPS33 expression and Macrophage M2 infiltration in GBM (rho = 0.393, p < 0.05). Table: 470P

Selected MRPs gene expression and GBM patient survival, HR > 1 suggests a harmful effect of the gene on survival

DE: Differential expression (GBM relative to normal) across GSE4290, GSE68848, and TCGA-GBM (overlap); U: Upregulated; D: Downregulated.

Conclusions

Our study identified a complex multi-omic framework through which MRPs are regulated and play their prognostic and tumorigenic roles in GBM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.