Methylated TIMP-3 DNA in Body Fluids Is an Independent Prognostic Factor for Gastric Cancer

Context.— Fluid methylated DNA may be a suitable biomarker for cancer patients. Objective.— To investigate whether circulating methylated tissue inhibitor of metalloproteinase 3 (TIMP-3) DNA in body fluids is a useful prognostic biomarker in gastric cancer (GC). Design.— TIMP-3 methylation was detected by real-time methylation-specific polymerase chain reaction in tumor tissues, paired preoperative peritoneal washes (PPWs), and paired serum samples from 92 GC patients. Results.— The frequency of TIMP-3 methylation was significantly elevated in GC tissues (63.04%; 58 of 92) compared with that in paired adjacent normal tissue (4.3%; 4 of 92) (P < .001). TIMP-3 methylation correlated closely with peritoneal metastasis and TNM stage (all P < .001). The frequency of TIMP-3 methylation in preoperative peritoneal washes and serum samples was 53.3% (49 of 92) and 58.7% (54 of 92), respectively. The Aζ values of the receiver operator characteristic curve for methylated TIMP-3 were 0.966 and 0.922 for serum and pre...