Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo, Japan.
Proteomics Clin Appl. 2010 May;4(5):560-7. doi: 10.1002/prca.200900172. Epub 2010 Feb 26.
We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients.
Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2-D DIGE consisted of 2250 protein spots.
Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p-value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2-D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting.
These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.
通过研究 12 例骨肉瘤（OS）患者活检样本的全蛋白表达谱，鉴定骨肉瘤化疗敏感性的新型生物标志物。
根据 Huvos 分级系统，将 6 例患者分为化疗效果好的患者组和化疗效果差的患者组。2-DE DIGE 获得的蛋白表达谱由 2250 个蛋白点组成。
其中，我们鉴定了 55 个蛋白点，其强度在两组患者之间有显著差异（经 Bonferroni 调整的 p 值<0.01）。质谱蛋白鉴定表明，这 55 个点对应 38 个不同的基因产物，包括过氧化物酶 2（PRDX 2）。使用针对 PRDX 2 的特异性抗体证实了 PRDX 2 在化疗效果好的患者组和化疗效果差的患者组之间的差异表达，而 Western blot 检测到的 PRDX 2 水平与相应的 2-DE DIGE 值高度相关。使用 Western blot 检测另外 4 例 OS 患者进一步证实了 PRDX 2 表达的预测价值。
这些结果确立了 PRDX 2 作为骨肉瘤化疗敏感性标志物的候选物。在治疗前对活检样本进行 PRDX 2 检测可能有助于骨肉瘤的更有效管理。
