Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression
Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression
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DOI：
10.4161/cbt.3.12.1238
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Hruban, RH
中科院分区：
文献类型：
--
作者：
Hustinx, SR;Cao, DF;Hruban, RH
基因表达系列分析（SAGE）是发现新的肿瘤标志物的有力工具。公开的正常和肿瘤组织的在线SAGE文库（http：//www.ncbi.nlm.nih.gov/SAGE/）最近已经扩大;此外，更完整的人类基因组注释和更好的生物计算技术已经大大改善了差异表达的SAGE“标签”对人类基因的分配。这些改进为我们提供了使用现有SAGE文库重新评估胰腺癌中全局基因表达的机会。将从六种胰腺癌产生的SAGE文库与从11种非肿瘤组织产生的SAGE文库进行比较。与正常组织文库相比，我们确定了453个SAGE标签在胰腺癌中差异表达，包括395个映射到已知基因和58个“未表征”标签。在分配给已知基因的395个SAGE标签中，223个在胰腺癌中过表达，172个表达不足。为了将58个未表征的差异表达的SAGE标签映射到基因，我们使用新开发的称为TAGmapper的资源（http://tagmapper.ibioinformatics.org）来鉴定16个额外的差异表达基因。7个基因的差异表达，涉及多个细胞过程，如信号转导（MIC-1），分化（DMBT 1和Neugrin）、免疫应答（CD 74）、炎症（CXCL 2）、细胞周期（CEB 1）和酶活性（激肽释放酶6），通过组织微阵列的免疫组织化学标记证实（激肽释放酶6、CD 74和DMBT 1）或通过RT-PCR（CEB 1、Neugrin、MIC 1和CXCL 2）。值得注意的是，Neugrin是使用TAGmapper正确分配其先前未表征的SAGE标签的基因之一，验证了该程序的实用性。通过重新访问更新和扩展的SAGE数据库，可以识别癌症类型中新的差异表达基因。TAGmapper应该被证明是一个强大的工具，发现新的肿瘤标志物，通过分配的非特征性SAGE标签。
Serial analysis of gene expression ( SAGE) is a powerful tool for the discovery of novel tumor markers. The publicly available online SAGE libraries of normal and neoplastic tissues (http://www.ncbi.nlm.nih.gov/SAGE/) have recently been expanded; in addition, a more complete annotation of the human genome and better biocomputational techniques have substantially improved the assignment of differentially expressed SAGE "tags" to human genes. These improvements have provided us with an opportunity to re-evaluate global gene expression in pancreatic cancer using existing SAGE libraries. SAGE libraries generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags. Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper ( http://tagmapper.ibioinformatics.org), to identify 16 additional differentially expressed genes. The differential expression of seven genes, involved in multiple cellular processes such as signal transduction (MIC-1), differentiation (DMBT1 and Neugrin), immune response (CD74), inflammation (CXCL2), cell cycle (CEB1) and enzymatic activity ( Kallikrein 6), was confirmed by either immunohistochemical labeling of tissue microarrays ( Kallikrein 6, CD74 and DMBT1) or by RT-PCR ( CEB1, Neugrin, MIC1 and CXCL2). Of note, Neugrin was one of the genes whose previously uncharacterized SAGE tag was correctly assigned using TAGmapper, validating the utility of this program. Novel differentially expressed genes in a cancer type can be identified by revisiting updated and expanded SAGE databases. TAGmapper should prove to be a powerful tool for the discovery of novel tumor markers through assignment of uncharacterized SAGE tags.