Toward Colorectal Cancer Biomarkers: The Role of Genetic Variation, Wnt Pathway, and Long Noncoding RNAs.

Colorectal cancer (CRC) is the third leading cause of death worldwide, comprising nearly 8% of cancer-related deaths per year. In South Korea, for example, CRC is the second most common cancer in men, and third in women. This study reports on the association of CRC with genetic variations in long noncoding RNAs, activators, and inhibitors of a cell proliferation pathway. Five normal colon mucosa tissue samples and their matched five-stage IV CRC samples were evaluated (dataset Gene Expression Omnibus accession: GSE50760). We identified more than 5000 differentially expressed genes (DEGs). The Wnt pathway had the greatest portion of DEGs, including activators, inhibitors, and associated long noncoding RNAs (lncRNAs), suggesting the importance of Wnt pathway in CRC. The following genes were aberrantly expressed: , , , , , , , , and . Notably, is known to silence , and inhibits the Wnt ligands to negatively regulate the pathway. The lncRNA positively regulates , while positively regulates and . We note that HOTAIR was unable to silence . and were found to be upregulated, which may explain the high expression of the targets. Furthermore, 10 single-nucleotide polymorphisms (SNPs) were identified in five of the candidate genes above. A possible novel SNP in , chr11:44619242T > C, was predicted to introduce a binding site. These SNPs are hypothesized to contribute to aberrant and discrepant regulation of the Wnt pathway in a context of CRC pathogenesis. These findings collectively inform future research on diagnostics and therapeutics innovation in CRC.