Application of cDNA microarrays to generate a molecular taxonomy capable of distinguishing between colon cancer and normal colon

Zou, Tong; Selaru, Florin M.; Xu, Yan; Shustova, Valentina; Yin, Jing; Mori, Yuriko; Shibata, David; Sato, Fumiaki; Wang, Suma; Olaru, Andreea; Deacu, Elena; Liu, Thomas C.; Abraham, John M.; Meltzer, Stephen J.

doi:10.1038/sj.onc.1205613

Cited by 132 publications

(91 citation statements)

References 30 publications

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“…Mainly advanced cancer has been analysed in gene expression profiling-based studies on colorectal cancer (Alon et al, 1999;Backert et al, 1999;Hegde et al, 2001;Kitahara et al, 2001;Notterman et al, 2001;Takemasa et al, 2001;Agrawal et al, 2002;Birkenkamp-Demtroder et al, 2002;Lin et al, 2002;Zou et al, 2002;Frederiksen et al, 2003;Muro et al, 2003;Tureci et al, 2003;Williams et al, 2003;Bertucci et al, 2004). Only a small number of adenoma and early invasive cancer tissues have been analysed in previous studies, and the issue of flat-and protruded-type adenoma tissues has not been directly addressed (Notterman et al, 2001;Agrawal et al, 2002;Lin et al, 2002;Williams et al, 2003).…”

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confidence: 99%

Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis

et al. 2005

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It is generally accepted that most colorectal carcinomas arise in pre-existing adenomas. Morphologically, colorectal adenomas can be divided into two groups, protruded type and flat type. The aim of this study was to clarify relevant alterations of gene expression associated with the early stage of colorectal carcinogenesis. Using cDNA array, we analysed the expression profiles of 550 cancerrelated genes in 36 colorectal adenomas (18 flat-type and 18 protruded-type adenomas) and 14 early invasive carcinomas. Among the 550 genes, we chose 32 genes the average expression levels of which were at least three-fold up-or downregulated in tumour tissues compared with levels in matched normal tissues. A total of 13 and 19 genes were identified as up-and downregulated genes in tumour tissues, respectively. Among the upregulated genes, the average expression levels of E1AF, bone morphogenic protein (BMP)-4, insulin-like growth factor (IGF)-2, inducible nitric oxide synthase (iNOS), tissue inhibitors of metalloproteinase (TIMP)-1, Smad4, and nm23 in tumour tissues were over five times higher than those in matched normal tissues. Colorectal adenomas and early invasive carcinomas were divided into two major clusters by clustering analysis. Moreover, flat-and protruded-type adenomas were divided into two major clusters by clustering analysis. The expression profiles obtained by the cDNA array clearly indicate that colorectal adenomas and early invasive carcinomas have specific expression profiles. Likewise, the gene expression profiles of flat-and protruded-type adenomas are different. These results indicate that molecular classification of early colorectal tumours by a cDNA array is feasible.

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confidence: 99%

Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis

et al. 2005

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“…Gene expression profiling-based studies of CRC have so far compared normal and tumour tissue samples or different stages of disease (Alon et al, 1999;Backert et al, 1999;Hegde et al, 2001;Kitahara et al, 2001;Notterman et al, 2001;Agrawal et al, 2002;Birkenkamp-Demtroder et al, 2002;Lin et al, 2002;Zou et al, 2002;Frederiksen et al, 2003;Tureci et al, 2003;Williams et al, 2003), but none has directly addressed the issue of prognosis or MSI phenotype. Here we have applied DNA microarray technology to analyse the expression of B8000 genes in 50 cancer and noncancerous colon tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

et al. 2004

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Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of B8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P ¼ 0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.

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“…As a complementary approach for identifying regulatory targets of hsa-miR-342 for future studies, we queried the Oncomine cancer profiling research database (www.Oncomine.org) (Rhodes et al, 2007) to identify genes that are (a) overexpressed in colorectal cancer based on results from three relevant gene expression profiling studies (Alon et al, 1999;Notterman et al, 2001;Zou et al, 2002) and (b) PicTar-predicted targets of hsa-miR-342. Eleven genes satisfied these criteria and are presented in Supplementary Table S3.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer

et al. 2008

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MicroRNAs are small, non-coding RNAs that influence gene regulatory networks by post-transcriptional regulation of specific messenger RNA targets. MicroRNA expression is dysregulated in human malignancies, frequently leading to loss of expression of certain microRNAs. We report that expression of hsa-miR-342, a microRNA encoded in an intron of the gene EVL, is commonly suppressed in human colorectal cancer. The expression of hsa-miR-342 is coordinated with that of EVL and our results indicate that the mechanism of silencing is CpG island methylation upstream of EVL. We found methylation at the EVL/hsa-miR-342 locus in 86% of colorectal adenocarcinomas and in 67% of adenomas, indicating that it is an early event in colorectal carcinogenesis. In addition, we observed a higher frequency of methylation (56%) in histologically normal colorectal mucosa from individuals with concurrent cancer compared to mucosa from individuals without colorectal cancer (12%), suggesting the existence of a 'field defect' involving methylated EVL/hsa-miR-342. Furthermore, reconstitution of hsa-miR-342 in the colorectal cancer cell line HT-29 induced apoptosis, suggesting that this microRNA could function as a proapoptotic tumor suppressor. In aggregate, these results support a novel mechanism for silencing intronic microRNAs in cancer by epigenetic alterations of cognate host genes.

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Application of cDNA microarrays to generate a molecular taxonomy capable of distinguishing between colon cancer and normal colon

Cited by 132 publications

References 30 publications

Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis

Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters

Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer

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