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首页> 外文期刊>Journal of Neuro-Oncology >Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR
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Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR

机译：原发性胶质母细胞瘤和非肿瘤性脑组织的基因表达谱分析：通过寡核苷酸微阵列和实时定量PCR识别潜在的靶基因

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摘要

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31–36 and 2 at 17q24–25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.
机译：胶质母细胞瘤的预后仍然非常差，发现新的分子治疗靶标对于优化治疗策略可能很重要。比较正常和肿瘤组织的基因表达分析已用于鉴定与肿瘤发生和潜在治疗靶点相关的基因。我们已经使用这种方法来识别原发性胶质母细胞瘤和非肿瘤性脑组织之间差异表达的基因。我们选择了20个与细胞周期，细胞运动和生长，增殖以及细胞间信号转导相关的过表达基因，并通过实时定量PCR分析了从20例原发性胶质母细胞瘤和10例原发性胶质母细胞瘤的新鲜切片中获得的cDNA中的表达水平。非肿瘤性白质组织样本。在分析的20个基因中，有18个在胶质母细胞瘤中的基因表达水平显着高于非肿瘤性白质：CDKN2C，CKS2，EEF1A1，EMP3，PDPN，BNIP2，CA12，CD34，CDC42EP4，PPIE，SNAI2，P <0.00001 GDF15和MMP23b； NFIA（P：0.0001），GPS1（P：0.0003），LAMA1（P：0.002），STIM1（P：0.006）和TASP1（P：0.01）。这些基因中的五个位于1p31–36的连续基因座中，位于17q24–25的两个基因中，其中8个编码表面膜蛋白。免疫组化检测PDPN和CD34蛋白表达，与PCR结果相符。目前的结果表明，在人类原发性胶质母细胞瘤中存在18个过表达的基因，这些基因可能在这些肿瘤的发病机理中发挥重要作用，并且值得作为新的治疗靶点进行进一步的功能研究。

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