Abstract
Ewing’s sarcoma (ES) is an extremely aggressive malignant bone tumor with a high incidence among children and adolescents. The immune microenvironment plays an important role in ES development. The aim of the current study was to investigate the immune microenvironment in ES patients to identify immune-related gene signatures. Single-sample gene set enrichment analysis (ssGSEA) was used to cluster the RNA sequences of 117 ES patients, and their immune cell infiltration data were downloaded and evaluated based on the Gene Expression Omnibus (GEO) database. High, medium, and low immune cell infiltration clusters were identified. Based on the comparison of clusters with high and low immune cell infiltration, normal skeletal muscle cells, and ES, we identified 198 common differentially expressed genes. GO and KEGG enrichment analyses indicated the underlying immune mechanism in ES. Cox and LASSO regression analyses were conducted to select immune-related prognostic genes. An external dataset from the International Cancer Genome Consortium (ICGC) was used to validate our results. Ten immune-related, independent prognostic genes (FMO2, GLCE, GPR64, IGFBP4, LOXHD1, PBK, SNAI2, SPP1, TAPT1-AS1, and ZIC2) were selected for analysis. These 10 immune-related genes signature were determined to exhibit independent prognostic significance for ES. The results of this study provide an approach for predicting the prognosis and survival of ES patients, and the elucidated genes may be a promising target for immunotherapy.
Highlights
Ewing’s sarcoma (ES) is an extremely aggressive malignant bone tumor with a high incidence among children and adolescents (Subbiah et al, 2009; Gupta et al, 2010)
We identified a 10 immune-related prognosis genes signature correlated with the prognosis in differentially expressed genes (DEGs) in both ES group and high immune cell infiltration cluster by Cox regression and least absolute shrinkage and selection operator (LASSO) regression
The samples were grouped into three clusters, namely high, middle, and low levels of immune infiltration
Summary
Ewing’s sarcoma (ES) is an extremely aggressive malignant bone tumor with a high incidence among children and adolescents (Subbiah et al, 2009; Gupta et al, 2010). Primary bone tumors account for 5% of all childhood and adolescent cancers. ES is the second most commonly reported primary bone tumor (Balamuth and Womer, 2010). In previous studies (Jiménez-Morales et al, 2009), immune-related genes and immune cells were found to be closely related to the occurrence and development of autoimmune diseases. The TNF-β-308a allele is a common genetic risk factor for the development of childhood immune and/or inflammatory diseases (JiménezMorales et al, 2009). Synovitis caused by rheumatoid arthritis is closely associated with the infiltration of various immune cells (Weyand and Goronzy, 2021)
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