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

BACKGROUND: Adenoma polyposis coli (APC) mutation is associated with tumorigenesis via the Wnt signaling pathway. AIM: To investigate the clinical features and mechanism of APC expression in gastric cancer (GC). METHODS: Based on APC expression profile, the related genome-wide mRNA expression, microRNA (miRNA) expression, and methylation profile in GC, the relationship between APC and GC, as well as the prognostic significance of APC were systematically analyzed by multi-dimensional methods. RESULTS: We found that high expression of APC (APC(high)) was significantly associated with adverse outcomes of T4 GC patients. Genome-wide gene expression analysis revealed that varying APC 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 APC 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 APC expression showed that there was differential methylation between the APC(high) and APC(low) 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 APC 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.