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尤文肉瘤的蛋白质组学研究现状。

Current Status of Proteomics in Ewing's Sarcoma.

机构信息

Division of Rare Cancer Research, National Cancer Center Research Institute, 104-0045 Tokyo, Japan.

出版信息

Proteomics Clin Appl. 2019 May;13(3):e1700130. doi: 10.1002/prca.201700130. Epub 2018 Aug 23.

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.

摘要

尤因肉瘤是一种极为罕见的骨间叶恶性肿瘤,主要发生在儿童和青少年。尤因肉瘤的特征是染色体易位,导致 EWS 基因与 ETS 家族的转录因子(如 EWS-FLI-1)形成嵌合融合。尤因肉瘤的临床结局仍然较差,需要新的治疗方法。蛋白质组学分析已被用于鉴定融合基因产物的功能,并提出了 EWS-FLI-1 周转的新机制。此外,蛋白质组学还揭示了 EWS-FLI-1 对 IL-6 分泌的调节作用,这可能促进肿瘤细胞的恶性行为。此外,蛋白质组学方法还用于评估特定基因和药物对尤因肉瘤的影响,并确定特定的生物标志物候选物,以预测耐药性和复发。通过鉴定与尤因肉瘤临床特征的分子背景相关的蛋白质,我们可以了解尤因肉瘤的生物学特性,并开发临床应用。需要肿瘤细胞和组织生物库和数据库等基础研究系统来有效利用有限的临床材料,并促进尤因肉瘤的研究。

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