Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human colorectal cancers with and without microsatellite instability identifies a set of discriminating genes and identifies proximal and distal cancers

ABSTRACT: Samples were taken from colorectal cancers in surgically resected specimens in 84 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes between MSI and MSS cancers and, furthermore, to determine the distinct characteristics of proximal and distal MSI cancers. Experiment Overall Design: Eighty-four colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures of MSI cancers, gene expression profiles were compared between MSI and MSS cancers. Next, we examined the difference in gene expression profiles between proximal and distal MSI cancers.

ORGANISM(S): Homo sapiens

SUBMITTER: Toshiaki Watanabe

PROVIDER: E-GEOD-4554 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Distal colorectal cancers with microsatellite instability (MSI) display distinct gene expression profiles that are different from proximal MSI cancers.

Watanabe Toshiaki T Kobunai Takashi T Toda Etsuko E Yamamoto Yoko Y Kanazawa Takamitsu T Kazama Yoshihiro Y Tanaka Junichiro J Tanaka Toshiaki T Konishi Tsuyosi T Okayama Yoshihiro Y Sugimoto Yoshikazu Y Oka Toshinori T Sasaki Shin S Muto Tetsuichiro T Nagawa Hirokazu H

Cancer research 20061001 20

Promoter methylation of the mismatch repair gene plays a key role in sporadic microsatellite instability (MSI) colorectal cancers. However, promoter methylation often occurs in proximal colon cancers, and molecular phenotypes underlying MSI cancers in distal colon have not been fully clarified. Our goal was to clarify the difference between MSI and microsatellite stability (MSS) cancers and, furthermore, to determine distinct characteristics of proximal and distal MSI cancers. By DNA microarray ...[more]

PMID: 17047040

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Project description:We have performed bioinformatic approaches to identify the level of enrichment between gene expression profiles characterizing MSI tumors and gene changes induced in vitro by the PARP-1 inhibitor Phenanthridinone and others using the Connectivity Map tool. In a first step, we have anyzed the expression of 300 colorectal cancers from the MECC study and generated a gene expression signature by microsatellite status. The criteria followed for selection of probe sets and detailed lists to be submitted subsequently to the Connectivity Map have been published previously by us in Clinical Cancer Research in 2009. In a second step, once we observed that deficiency in MRE11 exist among MSI tumors, our interest was focused on assessing if the homologous recombination pathway showed evidence of deregulation in MSI tumors. Therefore, we examined the expression levels of those genes integrated in the KEGG pathway hsa03440 using the previously generated gene expression data set. The dataset generated from our samples included a total of 300 colorectal fresh frozen tumors collected from the MECC study and were analyzed in two batches. The first batch was hybridized to the Affymetrix U133A chip and the second one to U133 Plus 2.0 (Supplementary Table S3). The final list of probe sets defining gene expression of MSI-H compared to MSS tumors was selected based on the strength of multiplicity adjusted P-values (cut-off P-value of < 0.001) and ratio of mean expression values across the two groups (cut-off Fold-change >1.3 and <0.7). It contained 442 upregulated and 480 downregulated probe sets. Then, MSI-H tumors present with changes in gene expression related to the homologous recombination pathway. Therefore, we examined the expression levels of those genes integrated in the KEGG pathway hsa03440 using the same data set. A total of 14 genes out of 30 were significantly differentially expressed in MSI-H compared to MSS tumors (Multiplicity adjusted Benjamini-Hochberg P-value<0.05). MRE11 and RAD50 probe sets showed a lower expression in MSI-H tumors and simultaneously other probe sets such as PARP-1 were significantly upregulated, probably secondary to the deficiency in the MRN complex proteins. This data provides evidence of significant differential expression of the homologous recombination pathway in MSI tumors.

Dataset Information

Transcription profiling of human colorectal cancers with and without microsatellite instability identifies a set of discriminating genes and identifies proximal and distal cancers

Publications

Distal colorectal cancers with microsatellite instability (MSI) display distinct gene expression profiles that are different from proximal MSI cancers.

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