Concurrent chemoradiotherapy (CCRT) followed by surgery is now the standard of treatment for advanced rectal cancers. The DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), has been reported to be involved in colorectal carcinogenesis. However, the clinical impact of MGMT expression on rectal cancers remained unclear. In this study, after examining tumor tissues from 172 patients with rectal cancer undergoing neoadjuvant CCRT, high MGMT expression was significantly correlated with advanced post-treatment tumor and node stages, and inferior tumor regression grade. Notably, high MGMT expression significantly appeared as an adverse predictor not only for recurrence-free survival (RFS) but also overall survival (OS). Moreover, high MGMT expression maintained an independent prognostic predictor for shorter RFS and OS. After combination treatment with irradiation and MGMT inhibitor, the rates of colony formation were decreased, and both annexin-V and gamma H2AX positive cells were increased in colorectal cancer cells, as compared with irradiation alone. These findings suggest novel therapeutic approaches targeting MGMT for rectal cancers.
