Objective  To investigate the clinical significance of the methylation status of RAS-like, estrogen-regulated growth-inhibitor (RERG) and zinc finger protein 671 (ZNF671) in plasma cell-free DNA (cfDNA) in nasopharyngeal carcinoma (NPC).

  Methods  A total of 106 patients with diagnosed and untreated NPC in Qionghai People's Hospital from February 2020 to March 2021 were selected as the NPC group. During the same period, 150 healthy volunteers were selected as the normal control group, and 100 patients diagnosed with chronic mucositis of the nasopharynx were selected as the benign control group. The RERG and ZNF671 promoter methylation status in plasma cfDNA and tissues was determined. The receiver operating characteristic (ROC) curve was used to analyze the value of the plasma cfDNA RERG and ZNF671 methylation status for the early diagnosis of NPC.

  Results  Plasma cfDNA RERG and ZNF671 promoter methylation rates and the degree of methylation were significantly higher in the NPC group than those in the benign and normal control groups (P<0.05). After the Kappa consistency test, the Kappa values of the tissue and plasma cfDNA RERG (45.28% vs. 38.68%, Kappa=0.788, P<0.001) and ZNF671 (55.66% vs. 48.11%, Kappa=0.791, P<0.001) promoter methylation rates were between 0.6 and 0.85, which were considered to be in good agreement. ROC curve analysis showed that the sensitivity, specificity, and area under the curve of the combined diagnosis based on the plasma cfDNA RERG and ZNF671 promoter methylation rate for NPC were 98.1%, 88.8%, and 0.981, respectively, which were better than those from the single diagnosis-based carcinoembryonic antigen.

  Conclusions  Combined evaluation of plasma cfDNA RERG and ZnF671 promoter methylation status may help in early diagnosis of NPC.