Establishment of 5-hydroxymethylcytosine expression model of circulating-free DNA gene in early diagnosis of nasopharyngeal carcinoma.

Abstract

e18047 Background: Nasopharyngeal carcinoma (NPC) has no obvious symptoms in the early stage of onset, and more than 65% of patients have been diagnosed as intermediate and advanced stage. Studies have shown that early diagnosis and timely treatment of NPC play a key role in the survival of patients.5-hydroxymethylcytosine (5hmC) as an important epigenetic modification of DNA is closely related to gene regulation and NPC pathogenesis. Objective: To clarify the diagnostic value of 5hmC expression in circulating free DNA (cfDNA) gene for NPC. Methods:The expression of 5hmC in cfDNA of 166 NPC and 165 controls was detected with high-throughput technology, and the differentially expressed gene map of 5hmC was drawn. Based on the screened 5hmC Top50 differentially expressed genes, the NPC diagnosis model was established with 70% of the sample size as the training set and 30% as the verification set. The efficacy of 5hmC in distinguishing NPC from healthy controls was evaluated by drawing the receiver operating characteristic curve (ROC) and calculating the sensitivity, specificity, area under the curve (AUC) and accuracy rate (AR). Results: High throughput detection showed that there were significant differences in 5hmC expression of 194 genes between NPC and control cfDNA, of which 185 genes were up-regulated and 9 down regulated in NPC. The results of diagnostic test show that when the Youden index threshold of 0.4749 at the verification set is taken as the cut-off value, the sensitivity, specificity, AUC and AR of the training set are 0.7652, 0.7304, 0.8250 and 0.7478, while in the verification set, they are 0.6863, 0.7400, 0.7388 and 0.7129 respectively. Conclusions: Our findings suggest that cell-free 5hmC signatures are valuable as potential noninvasive diagnostic biomarkers of NPC, which can be transformed into clinical application by further optimizing the diagnostic model.