Significant association between KDM1A promoter hypomethylation and colorectal cancer in Han Chinese

Abstract

Lysine-specific histone demethylase 1A gene (KDM1A) promotes tumorigenesis. The aim of this study was to investigate the association between KDM1A methylation and colorectal cancer (CRC). Currently, we collected 37 paired CRC tissues and adjacent non-tumor tissues from Jiangsu province and 75 paired CRC tissues and adjacent non-tumor tissues from Zhejiang province to conduct a two-stage experiment to study the association between KDM1A methylation and CRC. We used qMSP to measure the KDM1A promoter methylation, and the percentage of methylation reference (PMR) to quantify the KDM1A promoter methylation level. To investigate the effect of the selected KDM1A fragment on gene expression regulation, we also performed a dual luciferase reporter gene assay. In the stage I study, the KDM1A promoter methylation level in CRC tumor tissues was significantly lower than that in adjacent non-tumor tissues (median PMR: 6.93% vs 10.25%, P = 0.033). The results of the stage II study were similar to those of the stage I study (mean PMR: 12.94% versus 17.42%, P = 0.016). In addition, a clinical pathology subgroup analysis found that KDM1A hypomethylation was associated with CRC only in patients with well-differentiated CRC (stage I: P = 0.047; stage II: P = 0.040). The dual luciferase reporter assay showed that the transcriptional activity of the recombinant pGL3-KDM1A plasmid was significantly higher (fold change = 2, P = 0.0009). In conclusion, our results suggest that KDM1A hypomethylation is significantly associated with CRC.