CD200过表达对尤文肉瘤患者生存预后的影响

CD200 overexpression on the survival prognosis of Ewing's sarcoma

目的探讨CD200在尤文肉瘤中发挥的作用及其可能的机制,并寻找能改善尤文肉瘤患者生存预后的潜在药物。方法从国际癌症基因组联盟数据库中获取尤文肉瘤患者的RNA-seq及临床资料,采用生存分析探索CD200对尤文肉瘤患者生存预后的影响,进行基因集富集分析和Lincx分析寻找CD200促进尤文肉瘤恶性进程的分子机制和可能靶向CD200的抗尤文肉瘤药物,并通过RT-qPCR验证CD200的表达水平。结果CD200在尤文肉瘤细胞中显著过表达(P<0.05)。CD200低表达的尤文肉瘤患者生存期较高表达患者更长(P<0.05),CD200预测尤文肉瘤3年和5年预后的ROC曲线下面积>0.70,CD200表达水平是影响尤文肉瘤患者预后的独立危险因素(HR=1.102,95%CI:1.030~1.179,P=0.005)。CD200可能通过局部黏附、细胞因子与细胞因子受体相互作用、细胞外基质受体相互作用、上皮细胞间充质转化和TNF-α激活NF-κB等信号通路参与尤文肉瘤的恶性进展。卡麦角林、姜黄素、伊利司莫和恩扎妥林等对尤文肉瘤的临床治疗具有潜在应用价值。结论CD200是影响尤文肉瘤患者生存预后的独立风险因素,可作为尤文肉瘤预防、诊断和治疗的生物标志物。

Objective To explore the role of CD200 in Ewing's sarcoma and its possible pathological mechanisms,and to search for potential drugs that can improve the survival prognosis of Ewing's sarcoma patients.Methods The RNA seq and clinical data of Ewing's sarcoma patients were obtained from the International Cancer Genome Consortium database.The survival analysis was used to explore the impact of CD200 on the survival prognosis of Ewing's sarcoma patients.The gene set enrichment analysis(GSEA)and Lincx analysis were carried out to find the molecular mechanism of CD200 promoting the malignant process of Ewing's sarcoma and the anti-Ewing's sarcoma drugs that may target CD200.The expression level of CD200 was verified by RT qPCR.Results CD200 was significantly overexpressed in Ewing's sarcoma cells(P<0.05).The survival time of Ewing's sarcoma patients with low expression of CD200 was longer than high expression(P<0.05).The areas under the receiver operating characteristic curve in the 3-year and 5-year survival analysis were both greater than 0.70.CD200 expression level was an independent risk factor affecting the prognosis of Ewing's sarcoma patients.CD200 was involved in the malignant progression of Ewing's sarcoma through Focal adhesion,Cytokine-cytokine receptor interaction,ECM receptor interaction,Epithelial mesenchymal transition,and TNF-αsignaling via NF-κB.Cabergoline,curcumin,elesclomol,and enzastaurin had potential significance in the development and clinical application of drugs targeting CD200.Conclusion CD200 is an independent risk factor affecting the survival prognosis of Ewing's sarcoma patients,and it can be used as a biomarker for the prevention,diagnosis,and treatment of Ewing's sarcoma.