This hospital-based, prospective, case-controlled study was conducted on 68 patients, which included patients who had a normal endometrium (n = 18), hyperplasia of the endometrium (n = 24), and EC (n = 26). Methylation levels of the following genes were determined by using real-time methylation-specific polymerase chain reaction (PCR) amplification: zinc finger protein 177 (ZNF177), collagen type XIV 伪1 (COL14A1), dihydropyrimidinase-like 4 (DPYSL4), homeobox A9 (HOXA9), transmembrane protein with epidermal growth factor-like and two follistatin-like domains 2 (TMEFF2). The methylation index (MI) cutoff values for the different diagnoses were determined to test the sensitivity and specificity of the method and to generate the receiver operating characteristic (ROC) curves. The Mann–Whitney U test was used to test between-group differences in the MI.
The MI of the five genes was significantly higher in EC than the MIs in specimens of hyperplasia of endometrium and normal appearance (p < 0.001). The ROC analysis demonstrated that the sensitivity, specificity, and accuracy for detecting EC were 92.3%, 94.4%, and 95.1%, respectively, for ZNF177; 92.3%, 94.4%, and 95.7%, respectively, for COL14A1; 80.8%, 94.4%, and 81.4%, respectively, for HOXA9; 65.4%, 94.4%, and 89.5%, respectively, for TMEFF2; and 61.5%, 94.4%, and 63.3%, respectively, for DPYSL4. The combined testing of ZNF177 and COL14A1 had the best specificity (100%), but compromised sensitivity (88.5%).
Promoter methylation of ZNF177, COL14A1, HOXA9, DPYSL4, and TMEFF2 genes is a frequent epigenetic event in EC. Furthermore, the epigenetic hypermethylation of TMEFF2 may be a valuable marker for identifying undetected EC within endometrial hyperplasia.