# Clinical significance and oncogenic role of ECHDC2 in glioblastoma: a comprehensive analysis based on bioinformatics and in vitro experiments

## TL;DR

This study shows that high ECHDC2 levels are linked to worse outcomes in glioblastoma and that ECHDC2 promotes cancer growth and spread in lab experiments.

## Contribution

The study is the first to demonstrate ECHDC2's oncogenic role in glioblastoma through bioinformatics and in vitro validation.

## Key findings

- High ECHDC2 expression correlates with poor survival and aggressive features in glioblastoma patients.
- ECHDC2 knockdown reduces GBM cell proliferation and migration, while overexpression increases it.
- ECHDC2 is linked to immune cell infiltration and the PI3K/Akt signaling pathway in tumor progression.

## Abstract

Growing evidence implicates enoyl-CoA hydratase domain-containing protein 2 (ECHDC2) in oncogenesis, yet its role in glioblastoma (GBM) remains undefined. We aimed to clarify the pathological significance and molecular mechanisms of ECHDC2 in GBM.

Gene-expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed. Kaplan–Meier curves were used to evaluate the prognostic value of ECHDC2. Immune cell infiltration was quantified using CIBERSORT, single-sample gene-set enrichment analysis (ssGSEA), and ESTIMATE algorithms. Spearman’s correlation analysis was applied to assess the associations between ECHDC2 expression levels, immune checkpoint molecules, and immune cell subsets. To elucidate the functional relevance of ECHDC2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analyses (GSEA) were performed, while protein-protein interaction (PPI) networks were investigated using the STRING database. Subsequently, ECHDC2 was knocked down or overexpressed in GBM cell lines, and its effects on cell proliferation and migration were determined using CCK-8, EdU, wound-healing, and Transwell migration assays.

Upregulated ECHDC2 expression was significantly correlated with unfavorable clinicopathological features and reduced overall survival (OS) in patients with GBM. High ECHDC2 expression was associated with increased infiltration of effector-memory CD8+ T cells (TEM) and plasmacytoid dendritic cells (pDCs). Enrichment analyses demonstrated that ECHDC2 is involved in tumor progression, with a particular focus on the PI3K/Akt signaling pathway. In vitro experiments showed that ECHDC2 knockdown suppressed the proliferation and migration of GBM cells. Conversely, ECHDC2 overexpression exerted the opposite effects on GBM cell proliferation and migration.

ECHDC2 overexpression promotes GBM progression and portends poor prognosis. ECHDC2 may serve as both a prognostic biomarker and a therapeutic target in GBM.