Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

Automated summary

Colorectal cancer is a heterogeneous disease with genetic and epigenetic changes, and molecular assessment along with biomarker use for prognosis is gaining attention. This study identifies high mRNA levels of 10 upregulated genes in CRC cells and datasets, showing correlation with worse prognosis in CRC patients. CTNNB1 is found to be a key factor in the interaction with upregulated CRC-associated genes, particularly regulating NKD2, FOXQ1, and CEMIP, which when inhibited, can suppress CRC cell growth, providing efficient biomarkers for prognosis and a new molecular interaction network for CRC.