Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma
Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma
复制标题
DOI：
10.1002/gcc.20021
复制
发表时间：
2004-06-01
影响因子：
3.7
通讯作者：
Aburatani, H
中科院分区：
文献类型：
--
作者：
Takita, J;Ishii, M;Aburatani, H
为了研究早期和晚期神经母细胞瘤（NB）的各种遗传特征和差异，并识别参与NB进展的候选基因，我们对20种原发性肿瘤进行了DNA微阵列分析。基于1,700个基因中约500个基因表达模式的双向聚类分析揭示了这些III型肿瘤的遗传亚组。尽管13例早期肿瘤中的9例（69%）和6例晚期肿瘤中的4例（67%）被归类为同一簇，但其余肿瘤显示出不同的表达谱。这表明早期和晚期肿瘤都是异质性的。基于微阵列数据，我们确定了BIRC，CDKN 2D和SMARD 3基因作为那些主要在早期或晚期表达的基因。这些基因已被报道分别与细胞凋亡，细胞周期和转录激活因子相关。为了更好地评估这些基因在NB中的表达的预后价值，对50个原发性肿瘤进行实时聚合酶链反应。BIRC 3和CDKN 2D基因的表达在早期组中显著高于晚期组（分别为P = 0.002和0.003），而SMARD 3基因的表达在早期组中显著降低（P = 0.02）。因此，BIRC、CDKN 2D和SMARD 3基因可能成为NB的新型预后标志物。(C)2004 Wiley-Liss，Inc.
To investigate the various genetic characteristics of and differences between early- and advanced-stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two-way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these Ill tumors. Although 9 of the 13 early-stage tumors (69%) and 4 of the 6 advanced-stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early- and advanced-stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of l These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real-time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early-stage group than in the advanced-stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early-stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB. (C) 2004 Wiley-Liss, Inc.