Current Status of Proteomics in Ewing's Sarcoma

Abstract

Ewing's sarcoma is an extremely rare mesenchymal malignancy of the bone, which predominantly occurs in children and young adolescents. Ewing's sarcoma is characterized by chromosomal translocations resulting in the formation of chimeric fusions between the EWS gene and transcription factors of the ETS family, such as EWS-FLI-1. The clinical outcome of Ewing's sarcoma remains poor, and novel therapeutic approaches are required. Proteomic analyses have been applied to identify the functions of the fusion gene product, and a novel mechanism of EWS-FLI-1 turnover has been proposed. Furthermore, proteomics has revealed the regulation of IL-6 secretion by EWS-FLI-1, which may promote malignant behavior in tumor cells. In addition, proteomic approaches have been used to assess the effects of unique genes and drugs on Ewing's sarcoma and to determine specific biomarker candidates for the prediction of drug resistance and recurrence. By identifying the proteins relevant to the molecular backgrounds of clinical characters of Ewing's sarcoma, we can understand the biology of Ewing's sarcoma and develop clinical applications. Fundamental research systems such as tumor cell and tissue biobanks and databases are required to make effective use of the limited clinical materials and promote research into Ewing's sarcoma.

Current topics and management of head and neck sarcomas

“…Gene rearrangement and amplification can be detected by fluorescence in situ hybridization as a split or amplified signal, which is widely used in the routine pathological diagnosis of sarcomas. EWSR1-FLI1 and EWSR1-ERG rearrangements in Ewing’s sarcoma ( 21 , 22 ), DDIT3 gene rearrangements in myxoid liposarcomas ( 23 ), well-differentiated/dedifferentiated liposarcomas, MDM2 amplification in parosteal osteosarcomas and low-grade central osteosarcomas ( 24 ), and PAX3–FOXO1 and PAX7–FOXO1 rearrangement in alveolar RMS ( 25 ) are extremely important for diagnosis and prognostic estimation. Although studies are limited to malignancies in the head and neck region, recently, core needle biopsy (CNB) has also been applied for histopathological diagnosis ( 26 ).…”

Construction of a Prognostic Signature in Ewing’s Sarcoma: Based On Metabolism-Related Genes

“…At present, many studies have con rmed that metabolism is closely related to Ewing's sarcoma. For example, Tadashi Kondo [10] said that through proteomic analysis, they proposed a new mechanism for the occurrence and development of Ewing's sarcoma, that is, the EWS-FLI-1 transition, and pointed out that EWS-FLI-1 has a certain regulatory effect on IL-6 secretion, thereby promoting tumor growth and metastasis. The lack of EWS-FLI-1 can lead to the excessive secretion of IL-6 and other soluble factors, which activate STAT signaling in bystander cells that maintain EWS-FLI-1 expression, and these factors can prevent the spontaneous apoptosis of tumor cells [11] .…”