Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics
Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics
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DOI：
10.1158/1078-0432.ccr-08-1913
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发表时间：
2009-04-15
影响因子：
11.5
通讯作者：
Kondo, Tadashi
中科院分区：
文献类型：
--
作者：
Kikuta, Kazutaka;Tochigi, Naobumi;Kondo, Tadashi
目的：通过研究尤文肉瘤患者的整体蛋白质表达谱，寻找新的尤文肉瘤预后生物标志物。实验设计：采用双向差示凝胶电泳法对8例尤文肉瘤患者的活检标本进行蛋白质组学分析。3例患者初诊后3年内存活并连续无病生存(预后良好组)，5例患者在初诊后2年内死亡(预后不良组)。结果：双向差异凝胶电泳法得到的蛋白质表达谱由2,364个蛋白质点组成，其中66个蛋白质点的强度在两组之间相差2倍。蛋白质的质谱学鉴定表明，这66个点对应于53个不同的基因产物。通径分析显示，53种蛋白质中有31种与骨组织肿瘤显著相关(P<；0.000001)。用免疫组织化学方法对34例尤文肉瘤患者进行了核磷脂的预后评估。单因素和多因素分析显示，核磷蛋白表达与总生存期显著相关(P<；0.01)。结论：核磷蛋白可作为尤文肉瘤患者的独立预后标志物。在治疗前检测活检样本中的核磷蛋白可能有助于尤文氏肉瘤的有效治疗。
Purpose: We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients.Experimental Design: We examined the proteomic profile of eight biopsy samples from Ewing's sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group).Results: The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed >2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P < 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing's sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P < 0.01).Conclusions: These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing's sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing's sarcoma.