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Differential proteomic profiling of chordomas and analysis of prognostic factors.

机译:脊索瘤的蛋白质组差异分析和预后因素分析。

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摘要

BACKGROUND: The recurrence rate of chordoma is high, and the prognosis is poor. METHODS: Differential proteomic analysis was performed on chordomas and adjacent normal tissues, with verification by Western blot. Protein expression was evaluated by immunohistochemistry of 37 chordomas. Association of candidate protein expression with clinical parameters, disease-free survival, and overall survival were analyzed. RESULTS: We identified 14 up-regulated and 5 down-regulated proteins in chordomas. Expression of alpha enolase (ENO1), pyruvate kinase M2 (PKM2), and gp96 was higher in recurrences than in primary tumors. Univariate analysis showed that significantly adverse factors for disease-free survival were overexpression of ENO1 and PKM2, involvement of contiguous vertebral levels, and inadequate surgical margin at initial surgery. Inadequate surgical margin without radiotherapy, involvement of contiguous vertebral levels, and cervical spine location were adverse factors for overall survival. By multivariate analysis, independent adverse prognostic factors were inadequate surgical margin and involvement of multiple contiguous vertebral levels for recurrence; upper cervical spine location and involvement of contiguous vertebral levels for tumor-related death. Multivariate analysis failed to show the significance of the proteins. CONCLUSIONS: Involvements of multiple contiguous vertebral levels and upper cervical spine, rather than overexpression of ENO1, PKM2, or gp96, are independent prognostic indicators for chordomas.
机译:背景:脊索瘤复发率高,预后差。方法:对脊索瘤和邻近的正常组织进行差异蛋白质组学分析,并通过蛋白质印迹法进行验证。通过37个脊索瘤的免疫组织化学评估蛋白质表达。分析候选蛋白表达与临床参数,无病生存期和总生存期的关联。结果:我们在脊索瘤中鉴定出14种上调蛋白和5种下调蛋白。与原发性肿瘤相比,α-烯醇化酶(ENO1),丙酮酸激酶M2(PKM2)和gp96的表达更高。单因素分析表明,无病生存的显着不利因素是ENO1和PKM2的过表达,连续椎骨水平的介入以及初次手术时手术余量不足。没有放疗的手术切缘不足,连续椎体水平受累以及颈椎位置都是整体生存的不利因素。通过多变量分析,独立的不良预后因素是手术切缘不足和累及多个连续椎骨水平的复发。上颈椎的位置和邻近椎骨水平的受累与肿瘤相关的死亡。多变量分析未能显示蛋白质的重要​​性。结论:累及多个连续椎体水平和上颈椎而不是ENO1,PKM2或gp96的过表达是脊索瘤的独立预后指标。

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