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

• Main Authors: Claus-Dieter Mayer, Soizick Magon de La Giclais, Fozan Alsehly, Stefan Hoppler
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Genes
• Subjects: Wnt; colorectal cancer; TCF; LEF; transcriptome
• Online Access: https://www.mdpi.com/2073-4425/11/5/538

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.