477P - ENHO's protective role in lower grade glioma

Background

Lower grade gliomas (LGGs) represent 15% of all primary brain tumors, and have variable prognosis. The prognostic influence of the ENHO gene in LGGs remains elusive, necessitating further bioinformatic exploration to improve patient management and outcomes.

Methods

Differential gene expression based on High/low ENHO expression was extracted using the “DESeq2” R package. Immune infiltration, mutational burden, gene set variation analysis (GSVA) and drug resistance were analyzed through GSCALite and cBioPortal. Additional immune infiltration and survival analysis used TIMER2.0. Gene set enrichment analysis (GSEA) was conducted via TCGAbiolinks and enriched further using Enrichr.

Results

Multivariate overall survival (OS) analysis showed a protective effect for ENHO (HR = 0.58, p <0.001). GSVA for OS and progression-free survival (PFS) for co-expressed genes and upregulated genes also showcased favorable prognosis OS:(HR = 0.40, p<0.001) and (HR = 0.34, p<0.001), respectively; PFS: (HR = 0.53, p<0.001) and (HR = 0.44, p<0.001), respectively. Survival GSVA of downregulated genes revealed an association with worse OS (HR = 4.19, p < 0.001) and PFS (HR = 2.45, p< 0.001). GSVA for upregulated genes showed a negative correlation with DNA damage, EMT, and PI3KAKT pathways. GSVA for downregulated genes had a positive correlation with EMT, DNA damage, and PI3K/AKT pathways. GSVA for co-expressed genes revealed significant negative correlations with DNA damage and EMT pathways. Mutational burden analysis revealed that shallow deletion is the most common ENHO mutation among all LGG subtypes, regardless of stage. Immune infiltration analysis for ENHO, upregulated, and co-expressed genes showcased the infiltration of: Central memory B cells, CD8 T cells, Neutrophils, and CD4 T cells. Decreased infiltration of cancer associated fibroblasts was observed for high ENHO expression. GSEA of coexpressed genes revealed significant involvement in cell cycle processes and regulation.

Conclusions

ENHO's role in LGG is yet to be determined, but our results showcase a possible protective effect through its modulation of the immune system, cell cycle signalling, and EMT pathways. Primary studies are still needed to validate ENHO's role in LGG.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.