Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Methylation-silenced genes in colorectal cancer cell lines

ABSTRACT: Using an oligonucleotide array, we undertook a genome-wide search for genes upregulated following treatment with a demethylating agent in two CRC cell lines. Promoter methylation status was determined in 12 CRC cell lines and 11 CRC tissues. After the treatment, 350 genes were upregulated 1.5 fold or more. Six genes (PAGE-5, VCX, MAEL, GAGED2, UCHL1, and GAGE7), which contained putative 5'CpG islands in their promoter regions, were confirmed to be silenced in CRC cell lines. The median level of UCHL1 gene expression in cell lines with methylation was significantly lower than that in cell lines without methylation (P = 0.032). The level of methylation of UCHL1 was significantly higher in tumors than in corresponding normal mucosae (P = 0.005). Chemical genomic screening led to the identification of a specific promoter subject to hypermethylation in CRC. These results suggest that aberrant promoter methylation is the primary mechanism of transcriptional silencing of the UCHL1 gene and that methylation of the UCHL1 gene promoter increases during the development and progression of CRC Keywords: Methylation Analysis This study explored methylation-silenced genes in colorectal cancer (CRC) cell lines. Using an oligonucleotide array, a genome-wide search for genes upregulated following treatment with a demethylating agent, 5-aza-2â??-deoxycitidine, in two CRC cell lines, DLD-1 and HT-29, was performed. Promoter methylation status of candidate genes silenced and upregulated following the treatment was determined in 12 CRC cell linesby methylation-specific PCR.

ORGANISM(S): Homo sapiens

SUBMITTER: Satoshi Fukutomi

PROVIDER: E-GEOD-7687 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of methylation-silenced genes in colorectal cancer cell lines: genomic screening using oligonucleotide arrays.

Fukutomi Satoshi S Seki Naohiko N Koda Keiji K Miyazaki Masaru M

Scandinavian journal of gastroenterology 20071201 12

<h4>Objective</h4>Aberrant methylation of promoter CpG islands is associated with the loss of expression of tumor suppressor genes in human cancers. The purpose of this study was to examine methylation-silenced genes in colorectal cancer (CRC) cell lines.<h4>Material and methods</h4>Using an oligonucleotide array, we undertook a genome-wide search for genes upregulated following treatment with a demethylating agent (5-aza-2'-deoxycytidine) in two CRC cell lines, DLD-1 and HT29. Promoter methylat ...[more]

PMID: 17994469

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Project description:Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we identified neurotensin, highly expressed in HNSCCs in comparison with normal tissues, as an invasion-promoting factor in HNSCC by using microarray analysis of clinical samples. Indeed, neurotensin overexpression associated with lymph node metastasis of neck, and tumors exhibiting neurotensin overexpression had a poor distant metastasis-free survival rate. In HNSCC cells which expressed neurotensin receptor 1 (NTSR1), neurotensin promoted cellular invasion, migration, and induction of matrix metalloproteinases transcripts. Disruption of NTSR1 signaling by silencing RNA caused the reversion of the invasion of HNSCC cells. By further microarray analysis using neurotensin-treated cells, neurotensin caused increased expression of genes implicated in tumor progression and metastasis including cell growth, migration, invasion, adhesion, angiogenesis, and apoptosis. Our findings have revealed a critical role of neurotensin/NTSR1 for invasion and migration in the metastatic process of HNSCC. This study raises the possibility that neurotensin/NTSR1 could be used as a possible predictive marker and a molecular therapeutic target in the antimetastatic strategies of HNSCC. Keywords: Identification of a novel therapeutic target for head and neck squamous cell carcinomas A total of 21 primary HNSCC samples were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). 21 samples of normal-appearing mucosa at the margin of the surgical resection several centimeters from the tumor were also collected and designated histologically normal mucosa. 21 HNSCCs and paired normal tissues were used for microarray experiment. The clinicopathological grade was classified according to the criteria of the Japan Society for Head and Neck Cancer. The Ethics Committee of Chiba University approved our study, and informed consent was obtained from all patients for use of their tissue samples and clinical data. Tissue samples were immediately snap frozen in liquid nitrogen and stored at -80Â°C until use.

Project description:Background & Aims. The current staging system for colorectal cancer (CRC) based on TNM classification allows prediction of potential recurrence. However, it does not necessarily make reliable personalized prediction of prognosis. In this paper we describe combination of clinicopathological data and gene signature of dissected tumor specimen with stage II and III CRC patients would improve the situation.. Methods. A total of 1978 CRC were collected over 5 years, and then 371 stage II and 322 stage III of them with more than 45.9 months records were subjected to clinicopathological feature analyses. Out of this collection, 129 stage II and III CRC cases were selected for analyses of gene expression profiles with resected specimen. The gene signatures were analyzed by repeated random divisions of the samples into training and test sets to extract discriminator genes. After testing the applicability of this discriminator set, it was subjected to validation using a newly obtained set of 69 samples. Results. The pathological factors in solo or in combinations could not make personalized recurrence prediction, except for partial success with stage II patients. The gene signature, on the other hand, was capable of producing a set of discriminator genes, though the accuracy was yet to be improved. We observed that the best result was obtained when discriminators were selected from stage II CRC samples and used for prognosis of stage II CRC. When stage III cases were included in the process of discriminator extraction or in the process to validate samples, the results were poorer. Finally, we examined 31 independent stage II samples with a set of 30 such discriminators and were able to obtain results with 78 % accuracy, 90 % negative predictive value (NPV), and 55% positive predictive value (PPV). Conclusions. Independent clinicopathological variables were not able to predict prognosis of individual patient, unless the factors are combined. On the other hand, gene signatures allowed accurate prediction of prognosis for individuals, especially with stage II CRC, suggesting its potential use for selection of best treatment option for individual patients. The accuracy of discriminator prediction will be further improved when we take the evolution of CRC into consideration. Of 198 samples, 129 represented the discovery phase and 69 represented the validation phase.

Dataset Information

Methylation-silenced genes in colorectal cancer cell lines

Publications

Identification of methylation-silenced genes in colorectal cancer cell lines: genomic screening using oligonucleotide arrays.

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