多唾液酸神经细胞黏附分子（PSA-NCAM）是胶质母细胞瘤的一个预后不良因素，并调节神经胶质瘤细胞系中 olig2 的表达。
Polysialic acid neural cell adhesion molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines.
机构信息
Université de la Méditerranée CNRS UMR6216, Institut de Biologie du Développement de Marseille Luminy, Marseille, France.
出版信息
BMC Cancer. 2010 Mar 10;10:91. doi: 10.1186/1471-2407-10-91.
BACKGROUND
Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS).
METHODS
We set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05.
RESULTS
We showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis.
CONCLUSION
PSA-NCAM represents a valuable biomarker for the prognosis of GBM patients.
背景
多形性胶质母细胞瘤（GBM）是最具侵袭性和最常见的脑肿瘤，尽管目前尚无治愈方法。尽管患者的平均生存时间仅为一年，但预后存在显著差异。评估生物标志物有助于更好地了解这种类型的肿瘤，有助于预测预后、设计和评估治疗方法。神经发育性多聚唾液酸神经细胞黏附分子（PSA-NCAM）蛋白在多种癌症中过度表达。在这里，我们研究了其在 GBM 中的表达，并评估了其对总生存期（OS）和无病生存期（DFS）的预后价值。
方法
我们建立了一种用于 PSA-NCAM 定量的特异性和敏感的酶联免疫吸附试验（ELISA）检测方法，该方法与 PSA-NCAM 的免疫组织化学半定量分析相关性良好，因此为分析的 56 例 GBM 活检提供了 PSA-NCAM 含量的准确定量测量。对于统计学分析，采用 Spearman 相关系数来评估免疫组织化学和 ELISA 数据之间的一致性。使用 Kaplan-Meier 方法估计患者的生存情况，并使用对数秩检验比较曲线。在多变量分析中，使用 cox 回归比例风险模型评估潜在风险因素对 DFS 和 OS 的影响。统计显著性的阈值为 p = 0.05。
结果
我们发现 PSA-NCAM 在大约三分之二的 GBM 中以不同水平表达。在单变量分析中，PSA-NCAM 含量是 OS（p = 0.04）和 DFS（p = 0.0017）的不良预后因素。在多变量分析中，PSA-NCAM 表达是 OS（p = 0.046）和 DFS（p = 0.007）的独立负预测因子。此外，在神经胶质瘤细胞系中，PSA-NCAM 水平的表达与 olig2 的表达相关，olig2 是一种与胶质瘤发生相关的转录因子。
结论
PSA-NCAM 是 GBM 患者预后的有价值的生物标志物。
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