Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southeast Asia, especially in southern China. There were about 129,000 new NPC cases and 34,000 deaths worldwide in 2018 according to Global Cancer Obsercatory. Even though NPC is sensitive to radiotherapy and has a 5-year survival rate of about 70%, the prognosis is poor in advanced stage. Therefore, it is important to screen NPC in the early stage. Epstein–Barr virus (EBV) infection plays important roles in the development of NPC, and EBV immunological assay is employed as a standard diagnostics of NPC, however, it is an invasive method. DNA methylation may lead to tumor initiation and progression by dysregulation of specific genes, should be a potential biomaker for NPC screening in early stage in a non-invasive format by collecting sample using the nose swab.
48 paraffin embedded NPC and 36 chronic nasopharyngitis (CN) speciments were collected from the First Affiliated Hospital of Guangdong Pharmaceutical University, China, and EBV serum antigen were assayed for all these patients. The quantitative methylation-sensitive PCR (qMS-PCR) assays were employed to analyse the methylation of HIST1H4F, Septin9 and RASSF1, after bisulfite modification of DNA which was extracted from the paraffin embedded samples using QIAamp DNA FFPE Tissue Kit. The individual and combination methylation gene results were compared with the antibody titer of EBV serum antigen on the basis of pathology.
EBV serum antigen was positive in 59% of patients with NPC. The percent of patients with hypermethylation of the genes HIST1H4F, Septin9 and RASSF1 in NPC group was 69%, 67% and 60% respectively, which were higher than patients with CN with the positive rate under 30%. Interestingly, The positive rate leapt to 90.5% (19/21) when combination of these three hypermethylated genes in patients, which was more than using EBV serum antigen with the positive rate about 63% (P=0.02).
The combination of the hypermethylation of the genes HIST1H4F, Septin9 and RASSF1 may provide a potential biomarker for nasopharyngeal carcinoma screening in early stage.
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