Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profile upon forced Notch1 activation in LS174T cells

ABSTRACT: The cell line was modified to express activated form of Notch1 (NICD1 of mouse origin) upon Doxycycline addition to the culture medium generated by T-rex system (invitrogen) following manufacturer's instruction. Keywords: Genetic modification Pulse-chase experiment, examining expression profile at 0h, 12h, 24h from Doxycycline addition. For details, please refer to our publication (American Journal of Physiology GI and Liver disease, e-pub at Nov 20th, 2008)

ORGANISM(S): Homo sapiens

SUBMITTER: Tetsuya Nakamura

PROVIDER: E-GEOD-10136 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Requirement of Notch activation during regeneration of the intestinal epithelia.

Okamoto Ryuichi R Tsuchiya Kiichiro K Nemoto Yasuhiro Y Akiyama Junko J Nakamura Tetsuya T Kanai Takanori T Watanabe Mamoru M

American journal of physiology. Gastrointestinal and liver physiology 20081120 1

Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including the intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that Notch signaling is activated in a greater number of intestinal epithelial cells in the inflamed mucosa of colitis. Inhibition of Notch activation in vivo using a gamma-secretase inhibitor resulted in a severe exacerbation of the colitis attributable to the loss of th ...[more]

PMID: 19023031

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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

Gene expression profile upon forced Notch1 activation in LS174T cells

Publications

Requirement of Notch activation during regeneration of the intestinal epithelia.

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