Comprehensive analysis of multi Ewing sarcoma microarray datasets identifies several prognosis biomarkers

Abstract

Ewing sarcoma (ES) is a common primary malignancy in children and adolescents. Progression of treatment methods hasn't contributed a lot to the imrovement of prognosis. To identify potential prognostic biomarkers, a meta-analysis pipeline of multi-gene expression datasets for ES from the Gene Expression Omnibus (GEO) was performed. Three datasets were screened and differential expression genes (DEGs) in ES samples compared with normal tissues were identified through limma package and subjected to network analysis. As a result, 1,470 DEGs were obtained which were mainly involved in biological processes associated with immune response and transcription regulation. Network analysis obtained 22 core genes with high network degree and fold change. Kaplan-Meier analysis based on ES datasets from The Cancer Genome Atlas identified five genes, including glycogen phosphorylase, muscle-associated, myocyte-specific enhancer factor 2C, tripartite motif containing 63, budding uninhibited by benzimidazoses1 and Ras GTPase-activating protein 1, whose altered expression profiles are significantly associated with survival. Changes of their expression values were further confirmed through RT-qPCR in ES cell and normal cell lines. Those genes may be considered as potential prognostic biomarkers of ES and should be helpful for its early diagnosis and treatment.

Mutational landscape of primary and recurrent Ewing sarcoma

“…A low tumor mutational burden (TMB) is a general feature of sarcomas and other pediatric cancers. In our cohort, all patients had low TMB (< 10 mut/Mb), consistently with previous studies [ 14 , 18 , 24 ]. In other studies, relapsed tumors showed a 2- to 3-fold increased number of mutations [ 25 ]; however, probably due to a low number of relapsed/metastatic cases, we did not confirm this observation.…”

“…This is due to the oncogenic driving translocation between the EWSR1 gene and ETS family transcription factors that dominated the ES genetic landscape [11]. The most common fusion is EWSR1-FLI, observed in 80-85%, followed by EWSR1-ERG fusion [11,[14][15][16]. Besides characteristic fusion, additional pathogenic point mutations are observed in numerous genes, with the most common loss-offunction mutations in STAG2, TP53, and CDKN2A genes.…”

Molecular and biologic biomarkers of Ewing sarcoma: A systematic review

“…A meta-analysis of data by Yin et al found that PYGM , MEF2C , and TRIM63 were also downregulated, and their expression was positively associated with survival rates in ES [33] . However, BUB1B (a member of spindle assembly checkpoint protein) and RACGAP1 (a component of central spindle and essential for cytokinesis induction), both upregulated in ES, were negatively associated with survival rates of ES.…”

In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues

“…ES is one of a few tumors that display profound PAS+ staining during histopathological analyses, demonstrated to be glycogen through an additional step of diastase treatment (Schajowicz, 1959; Telles et al , 1978). In fact, glycogen metabolic enzymes are drastically altered by EWS‐FLI1 (Tanner et al , 2017; Aynaud et al , 2020), including the glycogen phosphorylase muscle isoform ( PYGM ; Yin et al , 2018). The MALDI‐MSI method confirms extensive glycogen accumulation in ES tumors.…”