Hypermethylation of APC2 Is a Predictive Epigenetic Biomarker for Chinese Colorectal Cancer

OBJECTIVE: To investigate methylation of the adenomatosis polyposis coli homologue (APC2) promoter and its correlation with prognostic implications in Chinese colorectal cancer (CRC). METHODS: The mRNA expression of APC2 in colorectal tissues was evaluated using the database of The Cancer Genome Atlas (TCGA). Methylation analysis of APC2 in tumor (n = 66) and corresponding adjacent formalin-fixed and paraffin-embedded (FFPE) tissues (n = 44) was performed by Sequenom EpiTYPER® and verified by cloning-based bisulfite sequencing analysis. Demethylation and retrieval of APC2 expression in cell lines HT29, HCT116, and SW480 were treated with 5-aza-2′-deoxycytidine (5-AZC). RESULTS: Analysis of TCGA showed that APC2 mRNA was significantly downregulated in primary tumors when compared to normal tissues (p < 0.05). APC2 methylation was upregulated (43.93% vs 7.31%, p < 0.05) in tumors compared to adjacent FFPE tissues. In vitro experiments demonstrated that 5-AZC downregulated the methylation of APC2 and retrieved its expression of mRNA and protein levels (p < 0.05). Multivariate Cox regression indicated that APC2_CPG_14 was an independent risk factor for overall survival (HR = 6.38, 95% CI: 1.59–25.64, p < 0.05). CONCLUSION: This study indicates that APC2 is hypermethylated and may be a tumorigenesis biomarker for Chinese CRC patients.