| Summary: | Aberrantly activated Wnt signaling causes cellular transformation that can lead to human colorectal cancer. Wnt signaling is mediated by Lymphoid Enhancer Factor/T-Cell Factor (LEF/TCF) DNA-binding factors. Here we investigate whether altered <i>LEF</i>/<i>TCF</i> expression is conserved in human colorectal tumor sample and may potentially be correlated with indicators of cancer progression. We carried out a meta-analysis of carefully selected publicly available gene expression data sets with paired tumor biopsy and adjacent matched normal tissues from colorectal cancer patients. Our meta-analysis confirms that among the four human <i>LEF</i>/<i>TCF </i>genes, <i>LEF1</i> and <i>TCF7</i> are preferentially expressed in tumor biopsies, while <i>TCF7L2</i> and <i>TCF7L1</i> in normal control tissue. We also confirm positive correlation of <i>LEF1</i> and <i>TCF7 </i>expression with hallmarks of active Wnt signaling (i.e., <i>AXIN2</i> and <i>LGR5</i>). We are able to correlate differential <i>LEF</i>/<i>TCF </i>gene expression with distinct transcriptomes associated with cell adhesion, extracellular matrix organization, and Wnt receptor feedback regulation. We demonstrate here in human colorectal tumor sample correlation of altered <i>LEF</i>/<i>TCF </i>gene expression with quantitatively and qualitatively different transcriptomes, suggesting <i>LEF</i>/<i>TCF-</i>specific transcriptional regulation of Wnt target genes relevant for cancer progression and survival. This bioinformatics analysis provides a foundation for future more detailed, functional, and molecular analyses aimed at dissecting such functional differences.
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