High expression of is an unfavorable prognostic biomarker in T4 gastric cancer patients.

BACKGROUND

Adenoma polyposis coli () mutation is associated with tumorigenesis the Wnt signaling pathway.

AIM

To investigate the clinical features and mechanism of expression in gastric cancer (GC).

METHODS

Based on expression profile, the related genome-wide mRNA expression, microRNA (miRNA) expression, and methylation profile in GC, the relationship between and GC, as well as the prognostic significance of were systematically analyzed by multi-dimensional methods.

RESULTS

We found that high expression of ( ) was significantly associated with adverse outcomes of T4 GC patients. Genome-wide gene expression analysis revealed that varying expression levels in GC were associated with some important oncogenes, and corresponding cellular functional pathways. Genome-wide miRNA expression analysis indicated that most of miRNAs associated with high expression were downregulated. The mRNA-miRNA regulatory network analysis revealed that down-regulated miRNAs affected their inhibitory effect on tumor genes. Genome-wide methylation profiles associated with expression showed that there was differential methylation between the and groups. The number of hypermethylation sites was larger than that of hypomethylation sites, and most of hypermethylation sites were enriched in CpG islands.

CONCLUSION

Our research demonstrated that high expression is an unfavorable prognostic factor for T4 GC patients and may be used as a novel biomarker for pathogenesis research, diagnosis, and treatment of GC.