Diverse LEF/TCF Expression in Human Colorectal Cancer Correlates with Altered Wnt-Regulated Transcriptome in a Meta-Analysis of Patient Biopsies.

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 alteredLEF/TCFexpression 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 humanLEF/TCFgenes,LEF1andTCF7are preferentially expressed in tumor biopsies, whileTCF7L2andTCF7L1in normal control tissue. We also confirm positive correlation ofLEF1andTCF7expression with hallmarks of active Wnt signaling (i.e.,AXIN2andLGR5). We are able to correlate differentialLEF/TCFgene 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 alteredLEF/TCFgene expression with quantitatively and qualitatively different transcriptomes, suggestingLEF/TCF-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.