Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas
Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas
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DOI：
10.1158/0008-5472.can-06-1514
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发表时间：
2007-01-01
期刊：
影响因子：
11.2
通讯作者：
Ried, Thomas
中科院分区：
文献类型：
--
作者：
Grade, Marian;Hoermann, Patrick;Ried, Thomas
为了表征原发性结肠癌中整体转录失调的模式，我们使用寡核苷酸微阵列对73个肿瘤[Unio Internationale Contra Canadian II期（n = 33）和III期（n = 40）]进行了基因表达谱分析。对于30个肿瘤，表达谱与匹配的正常粘膜样品进行比较。我们确定了一组1,950个基因，在肿瘤和粘膜样品之间具有高度显著的失调（P <1 e-7）。这些基因的显着比例映射到20号染色体（P = 0.01）。17个基因在正常结肠粘膜和癌之间具有> 5倍的平均表达差异，包括MYC和HMGA 1（一种假定的癌基因）的上调。此外，我们确定了68个基因在淋巴结阴性和淋巴结阳性肿瘤之间显著差异表达（P < 0.001），其功能注释揭示了在细胞免疫应答和监视中发挥作用的基因的优势。在> 40个肿瘤和正常粘膜样品中使用定量实时逆转录-PCR验证了20个失调基因的微阵列衍生的基因表达水平，这些技术之间具有良好的一致性。最后，我们建立了一个特定的基因组不平衡，这是映射32个分析的结肠肿瘤比较基因组杂交，全球转录活性的改变之间的关系。以前，我们对原发性直肠癌进行了类似的分析。结肠癌和直肠癌的系统比较揭示了基因组失衡和转录失调的显著重叠，包括Wnt/β-连环蛋白信号级联的激活，表明相似的致病途径。
To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e-7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a > 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node-negative and lymph node-positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in > 40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/beta-catenin signaling cascade, suggesting similar pathogenic pathways.