Elevated Expression Of Mdr1 Associated With Line-1 Hypomethylation In Esophageal Squamous Cell Carcinoma

Background: The aim is to discuss the relationship of Line-1 methylation and the MDR1 expression in esophageal squamous cell carcinoma (ESCC). Methods: We analyzed the methylation level of Line-1 by quantitative real-time MSP, and the expression of MDR1 by real-time RT-PCR in 310 ESCC and corresponding non-tumor tissues. Results: We found that the methylation index (MI) of Line-1 decreased from 0.90 in non-tumor tissues toward 0.78 in ESCC. The cumulative survival was significantly shorter in ESCC patients with MI <= 0.78 (34 months) than that in patients with MI > 0.78 (43 months). There was a statistical difference between MI <= 0.78 and MI > 0.78 cases with these clinicopathologic parameters (age, AJCC stage, differentiation; P = 0.010, P < 0.0001, P = 0.015, respectively). These results implied that Line-1 hypomethylation could be more in ESCC patients with older, advanced tumor and poor differentiation group. Meanwhile, ESCC with demethylation of Line-1 were shown elevated MDR1 expression in tumor (Mean(-Delta Delta Ct) = 0.21), but ESCC with hypermethylation of Line-1 were considered to be decreased MDR1 expression in tumor (Mean(-Delta Delta Ct) = -0.86). Conclusions: Line-1 hypomethylation could be as a biomarker of poor prognosis in ESCC patients. MDR1 gene could be activated via epigenetic mechanisms with demethylation of Line-1 in ESCC, and enhance tumor progression.