Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

This study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80-23.1; P for trend <0.01) and 8.01 (95% CI, 1.92-33.4; P for trend <0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.