Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas
Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas
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DOI：
10.1038/sj.onc.1205518
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发表时间：
2002-06-13
期刊：
影响因子：
8
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Lin, YM;Furukawa, Y;Nakamura, Y
大多数结肠癌被认为是通过“腺瘤到癌序列”模型发展的。为了阐明这一途径的机制，我们分析了20个结直肠肿瘤（9个腺瘤和11个分化腺癌）的基因表达谱的cDNA微阵列代表23 040个基因，再加上激光捕获显微切割。对20个肿瘤表达谱的二维层次聚类分析正确地将癌组与腺瘤组分开。此外，我们确定了51个基因的表达通常上调，376个通常下调，在这两种类型的肿瘤，而不是正常的结肠上皮和50个其表达水平显着不同的腺瘤和癌。根据50个鉴别基因的表达谱，我们建立了一个评分系统，以区分腺瘤和癌。应用该评分系统评估另外5例结直肠肿瘤，正确预测了其组织学特征。本文报道的全基因组信息有助于更深入地了解结直肠肿瘤的发生，特别是腺瘤-癌的进展，并为开发诊断、治疗和最终预防结直肠癌的新策略提供指标。
Most colon cancers are thought to develop through the 'adenoma-to-carcinoma sequence' model. To elucidate the mechanisms underlying this pathway, we analysed gene-expression profiles of 20 colorectal tumors (nine adenomas and 11 differentiated adenocarcinomas) by means of a cDNA microarray representing 23 040 genes coupled with laser-capture micro dissection. A two-dimensional hierarchical clustering analysis of expression profiles of the 20 tumors correctly separated the carcinoma group from the adenoma group. Furthermore we identified 51 genes whose expression was commonly up-regulated, 376 that were commonly down-regulated in both types of tumors as opposed to normal colonic epithelium and 50 whose expression levels were significantly different between adenomas and carcinomas. On the basis of expression profiles of the 50 discriminating genes, we established a scoring system to separate adenomas from carcinomas. Application of this scoring system for evaluating five additional colorectal tumors correctly predicted their histological features. The genome-wide information reported here should contribute to a more profound understanding of colorectal tumorigenesis, particularly of adenoma-carcinoma progression, and provide indicators for developing novel strategies to diagnose, treat, and ultimately prevent colorectal carcinomas.