Association between colorectal cancer and the degree of ITGA4 promoter methylation in peripheral blood mononuclear cells

Abstract

Background: Colorectal cancer (CRC) evolves gradually due to the accumulation of genetic and epigenetic changes in the cells of the colonic epithelium. Transition from polyp to CRC usually occurs over a long period and this provides an ideal situation for screening and detection of the disease during its early asymptomatic stage. ITGA4 promoter methylation has been reported in many cancers. In this study, we examined ITGA4 promoter methylation status in peripheral blood mononuclear cells (PBMCs). Materials and methods: Two hundred patients with CRC and 200 healthy controls were recruited to this study. Methylation-quantification of endonuclease-resistant DNA (MethyQESD) was used for quantitative analysis of the samples. Results: Mean ITGA4 methylation in the CRC cases was significantly higher than that of controls (91.35 +/- 43.51 vs. 70.71 +/- 25.75). The area under the ROC curve for the diagnosis of CRC was 0.70 (95 CI: 0.64, 0.75). The ITGA4 methylation level > 92.34 was the optimal cut-off point to distinguish CRC cases from controls with sensitivity of 0.54 and specificity of 0.89. The predictive power of ITGA4 methylation for CRC detection in females was higher (AUC = 0.80, 95 CI: 0.73, 0.87) than for males (AUC = 0.62, 95 CI: 38.1, 56.0). Conclusion: Based on our results, mean ITGA4 methylation in CRC group was significantly higher than that of control group (91.35 +/- 43.51 vs. 70.71 +/- 25.75, P < 0.001). Also, in adjusted logistic regression model, higher value of methylated ITGA4 (> 92.34 vs. <= 92.34) was significantly related to increased risk of CRC (OR = 9.17, 95 CI: 5.18, 16.25). Therefore, evaluation of ITGA4 promoter methylation in PBMCs could be considered as a noninvasive suitable blood-based biomarker for CRC screening.