Identification of gene signatures for invasive XXXX cells.

@entity10793 @entity9618 @entity24487 @entity25261 @entity1841 @entity1476 @entity5 @entity20176 @entity70802 @entity18962 @entity1570 @entity14 @entity3
BACKGROUND: Gene signatures of sporadic @entity14 tissues and microdissected @entity14 cells were analyzed to identify stromal and @entity5 cell-specific markers, respectively. METHODS: Serial sections of frozen @entity14 (n=29) were subjected to RNA isolation of (1) entire tissue sections with a various @entity5 cell content and of (2) microdissected invasive @entity5 cells. Three matching samples of microdissected normal colorectal epithelial and invasive @entity5 cells were similarly obtained. RNA samples were analyzed using the HG95A and HG95Av2 GeneChip microarrays (Affymetrix). The microarray data was evaluated by established methods and validated by Q-RT-PCR. RESULTS: Unsupervised hierarchical cluster analysis of 18 sample pairs (training set) clearly distinguished @entity5 from microdissected @entity5 cells. A 149-gene signature was identified using statistical methods, which was then validated by a hierarchical clustering analysis of 11 independent sample pairs (test set). Genes specifically associated with microdissected invasive @entity5 cells were for example @entity25261 and @entity18962 . In contrast, genes associated with stromal cells were for example @entity1476 , @entity1570 and @entity70802 . Finally, a 65-gene signature distinguished normal colorectal epithelial cells and invasive @entity5 cells, including down-regulation of @entity1841 and @entity10793 mRNA expression as well as up-regulation of @entity20176 , @entity9618 , @entity24487 mRNA expression. CONCLUSIONS: Our approach allowed precise evaluation of molecular signatures in morphologically defined cell populations and identified novel target genes related to @entity5 interactions in @entity14 . The approach enables further analysis of gene signatures in different @entity5 areas and cell types, such as within invasive margins to decipher molecular mechanisms of @entity14 and @entity3 .
