Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression profiling shows differential functions and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma

ABSTRACT: Our microarray study validates characteristic functions of serrated adenocarcinoma (SAC) reported in the only previous study which was performed on patients from a dissimilar environmental and genetic background and using a different microarray platform. In our study, fascin1 and hippocalcin were validated at the mRNA and protein level as the best biomarkers reported so far for the distinction of SAC from conventional carcinoma and from colorectal carcinoma showing molecular and histological features of high-level microsatellite instability. In this study, we used gene expression arrays to investigate differences between two experimental classes: serrated and conventional carcinomas

ORGANISM(S): Homo sapiens

SUBMITTER: FRANCISCO GARCIA

PROVIDER: E-GEOD-36758 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:KLF2 is a Krüppel-like zinc-finger transcription factor required for blood vessel, lung, T-cell, and erythroid development. KLF2-/- mice die by embryonic day 14.5 (E14.5), due to hemorrhaging and heart failure. Embryonic -like globin gene expression is reduced in KLF2-/- embryos compared to wildtype (WT), and E10.5 erythroid cells exhibit abnormal morphology. Other KLF2 target genes were identified by comparing E9.5 KLF2-/- and WT yolk sac erythroid cells, using laser capture microdissection and microarray assays. One hundred and ninety-six genes exhibited significant differences in expression; eighty-nine of these are downregulated in KLF2-/- compared to WT. Genes involved in cell migration, differentiation and development are over-represented in the KLF2-regulated gene list. Previously identified erythroid-enriched regulatory genes such as reelin, adenylate cyclase 7, cytotoxic T lymphocyte-associated protein 2 alpha, and CD24a antigen are downregulated in KLF2-/- compared to WT. SOX2, a pluripotency factor in ES cells, is also a KLF2 target in embryonic erythroid cells. We investigated whether reelin, which has an established role in neuronal migration and proliferation, has a role in embryonic erythropoiesis. Luciferase reporter assays demonstrated that KLF2 directly transactivates the reelin promoter, but reelin mutant mice have no apparent abnormalities in embryonic erythroid morphology or globin gene expression. Timed-pregnant KLF2+/- females were anesthetized and sacrificed. E9.5 yolk sacs were dissected from the embryo, cryoprotected in 20% sucrose in PBS and frozen in OCT media. A small portion of the embryo tail was used for PCR genotyping. Eight micron KLF2-/- frozen yolk sac sections were obtained and laser capture microdissection (LCM) was used to isolate primitive erythroid precursors. For each biological replicate, 2 to 4 yolk sacs from 2 different litters were used. Total RNA was isolated from 4 different KLF2-/- erythroid samples and hybridized to Affymetrix 430 A 2.0 microarrays

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Expression profiling shows differential functions and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma

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