Receiver operating characteristic curve analysis of the tumor markers squamous cell carcinoma antigen, carbohydrate antigen 199, and carcinoembryonic antigen as well as methylation of the four genes as evaluated using plasma samples of patients with esophageal cancer. A and C: Receiver operating characteristic (ROC) curves of methylation of the four genes (A) and tumor markers (C) in 33 patients with esophageal adenocarcinoma. Area under the curve (AUC)-complex methylation = 0.737 [95% confidence interval (CI): 0.584–0.89], AUC-carbohydrate antigen 199 (CA199) = 0.408 (95%CI: 0.297–0.519), AUC-carcinoembryonic antigen (CEA) = 0.683 (95%CI: 0.572–0.793), AUC-CEA + CA199 = 0.693 (95%CI: 0.588–0.798), and AUC-tumor markers and SHOX2, RNF180, SEPTIN9, and EPO methylation = 0.798 (95%CI: 0.714–0.883); B and D: ROC curves of methylation of the four genes (B) and tumor markers (D) in 177 patients with squamous cell carcinoma (SCC). AUC-complex methylation = 0.824 (95%CI: 0.775–0.891), AUC-SCC antigen (SCCA) = 0.516 (95%CI: 0.448–0.583), AUC-CEA = 0.626 (95%CI: 0.557–0.695), AUC-SCCA + CEA = 0.648 (95%CI: 0.584–0.711), and AUC-tumor markers and SHOX2, RNF180, SEPTIN9, and EPO methylation = 0.864 (95%CI: 0.820–0.908).