Cathepsin D is a potential serum marker for poor prognosis in glioma patients
Cathepsin D is a potential serum marker for poor prognosis in glioma patients
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DOI：
10.1158/0008-5472.can-04-4134
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发表时间：
2005-06-15
期刊：
影响因子：
11.2
通讯作者：
Seki, N
中科院分区：
文献类型：
--
作者：
Fukuda, ME;Iwadate, Y;Seki, N
组织蛋白酶D是一种可从癌细胞中分泌的与蛋白质催化和组织重塑有关的酰基蛋白酶。为了确定一个潜在的血清胶质瘤标记物，我们研究了87个组织样本中组织蛋白酶D的基因表达水平，并测定了胶质瘤患者血清中的蛋白浓度。组织样本包括43例胶质母细胞瘤、13例间变性星形细胞瘤、22例星形细胞瘤和9例正常脑组织。实时荧光定量RT-PCR分析结果显示，随着胶质瘤级别的升高，组织蛋白酶D转录水平明显升高（P = 0.0466，胶质母细胞瘤和间变性星形细胞瘤; P = 0.0008，胶质母细胞瘤和星形细胞瘤; P = 0.0271，胶质母细胞瘤和正常脑组织，非配对t检验）。抗组织蛋白酶D抗体的免疫组化分析显示，高转录水平的肿瘤细胞中的密集和斑点状染色。组织蛋白酶D的低表达与胶质瘤患者的长期生存密切相关。组织蛋白酶D基因高表达的胶质母细胞瘤患者的生存期明显短于低表达的患者（P = 0.0104，Cox-Mantel log-rank检验），并且经常发生软脑膜播散（P = 0.0016，卡方检验）。多因素分析证实组织蛋白酶D表达水平是短生存期的独立预测因子（P = 0.0102，考克斯比例风险回归模型）。ELISA法测定血清组织蛋白酶D浓度显示，与低级别肿瘤相比，高级别胶质瘤患者血清组织蛋白酶D浓度显著升高（p = 0.0081，卡方检验）。这些结果共同表明，组织蛋白酶D可能是一个潜在的血清标记物，用于预测人类胶质瘤的侵袭性。
Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue, unpaired t test). Immunohistochemical analysis with anticathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, chi(2) test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (p = 0.0081, chi(2) test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.