Association of HOXA9 Promoter Hypomethylation With Colorectal Cancer

Abstract

Background: The HOXA9 gene encodes a DNA-binding transcription factor that is closely related to cancer, including colorectal cancer (CRC). In this study, we first explored whether HOXA9 promoter methylation was associated with CRC. Materials and Methods: Quantitative methylation-specific PCR (qMSP) was used to detect HOXA9 methylation levels in 76 patients with tumor tissues and paired adjacent non-tumor tissues. The percentage of methylation reference (PMR) was used to indicate the level of gene methylation. Results: Our results showed that the methylation level of HOXA9 in tumor tissues was significantly lower than that of matched adjacent non-tumor tissues (median PMR, 4.61% vs 10.04%, P = 0.003). The similar significant difference was also found in 45 pairs of CRC samples from the Cancer Genome Atlas (TCGA) database (cg21942490, P = 0.039; cg22055728, P = 0.001). In addition, TCGA data analysis also showed a significant inverse correlation between HOXA9 methylation level and its gene expression (r = -0.438, P = 3.71E-59). Data analysis from Gene Expression Omnibus (GEO) showed that cells treated with demethylating reagent significantly up-regulated HOXA9 expression (fold change > 1.76, P = 0.009). Conclusion: Our results showed that HOXA9 hypomethylation is significantly associated with the risk of CRC, and the molecular mechanism of HOXA9 hypomethylation-related carcinogenesis needs further study.