Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas

被引:158
作者
Lin, YM
Furukawa, Y
Tsunoda, T
Yue, CT
Yang, KC
Nakamura, Y
机构
[1] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Minato Ku, Tokyo 1088639, Japan
[2] Shin Kong Wu Ho Su Mem Hosp, Dept Internal Med, Taipei 11160, Taiwan
[3] RIKEN, Inst Phys & Chem Res, SNP Res Ctr, Minato Ku, Tokyo 1088639, Japan
基金
日本学术振兴会;
关键词
colon cancer; adenoma-carcinoma sequence; cDNA microarray; expression profile;
D O I
10.1038/sj.onc.1205518
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4120 / 4128
页数:9
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