Identifying prognosis and metastasis-associated genes associated with Ewing sarcoma by weighted gene co-expression network analysis

Ewing sarcoma (ES) is a highly malignant pediatric tumor with a low survival rate and a high rate of metastasis. However, there have been limited reports on the exploration of new biomarkers of ES. Therefore, the aim of the present study was to identify the potential hub genes associated with overall vital survival (OVS) and metastasis in ES. Traditional methods for identifying differentially expressed genes lack the in-depth information of mechanistic studies. In this study, a weighted co-expression network for ES was constructed through weighted gene co-expression network analysis to identify co-expression modules associated with clinical phenotypes. The hub genes in the metastasis- and OVS-related co-expression modules were extracted, and the association between the hub genes and patient OVS was verified in another independent Gene Expression Omnibus dataset. Functional annotations and protein-protein interaction analysis of co-expression modules were also used to understand the potential regulatory mechanisms. The results of the functional enrichment analysis revealed that the OVS-associated module was mainly enriched in the cell cycle and immune response, and the metastasis-associated module was enriched in metabolism. A total of four genes (proteasome subunit α4, L1 cell adhesion molecule, serine/threonine kinase receptor-associated protein and cytotoxic T-lymphocyte-associated protein 4) in the OVS-related module and two genes (calcium voltage-gated channel auxiliary subunit γ2 and γ-aminobutyric acid type B receptor subunit 2) in the metastasis-related module were selected as hub genes. Further research on the hub genes identified in the present study may contribute to the understanding of the mechanism of ES metastasis and progression.