Neurosurgery Unit, Giannina Gaslini Children's Research Hospital, Genoa, Italy.
Neuro Oncol. 2011 May;13(5):500-8. doi: 10.1093/neuonc/nor022. Epub 2011 Apr 12.
The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative- polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan-Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.
表面标志物 PROM1 被认为是肿瘤起始细胞的最重要标志物之一，其表达被认为是神经胶质瘤和其他恶性肿瘤的不良预后因素。迄今为止，据我们所知，尚未对髓母细胞瘤系列中 PROM1 表达进行专门研究。我们研究的目的是评估 PROM1 基因在髓母细胞瘤中的表达谱，并评估其作为预后因素的可能作用。通过使用特异性染料标记探针系统，在 45 个髓母细胞瘤样本中通过定量聚合酶链反应评估 PROM1 基因的表达。在预后较差的患者（P=.007）和转移患者（P=.03）中发现 PROM1 的表达显著更高。Kaplan-Meier 分析表明，与 PROM1 mRNA 水平较低的患者相比，PROM1 mRNA 水平较高的患者的总生存期（OS）和无进展生存期（PFS）均较短，即使排除促结缔组织增生型病例也是如此（P=.0004 和 P=.002，分别为所有病例的 OS 和 PFS；对于无促结缔组织增生型病例，分别为 P=.002 和 P=.008 的 OS 和 PFS）。Cox 回归模型表明，PROM1 表达是独立的预后因素（风险比，4.56；P=.008）。通过基于微阵列的分析在独立的 42 例病例队列中验证了该结果（P=.019）。这些结果表明，PROM1 的高 mRNA 水平与小儿髓母细胞瘤的不良预后相关。此外，高 PROM1 表达水平似乎增加了转移的可能性。这些结果需要在更大的前瞻性系列中得到证实，以便将 PROM1 基因表达纳入可能在临床环境中使用的风险分类系统。
