Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma

Cancer Epidemiol. 2013 Oct;37(5):708-13. doi: 10.1016/j.canep.2013.05.012. Epub 2013 Jun 20.

Abstract

Purpose: Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples.

Methods: cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared.

Results: The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC.

Conclusion: Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.

Keywords: Cell-free circulating DNA; DNA hypermethylation; Diagnosis; MSP; Nasopharyngeal carcinoma; Tumor suppressor genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • DNA Methylation*
  • DNA, Neoplasm / blood*
  • DNA, Neoplasm / genetics*
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Death-Associated Protein Kinases / blood
  • Death-Associated Protein Kinases / genetics
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / virology
  • Female
  • Genes, Tumor Suppressor*
  • Genes, p16
  • Herpesvirus 4, Human / genetics
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / blood*
  • Nasopharyngeal Neoplasms / diagnosis
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / virology
  • Neoplastic Cells, Circulating*
  • Promoter Regions, Genetic
  • Tumor Suppressor Proteins / blood
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / blood
  • Ubiquitin Thiolesterase / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DLEC1 protein, human
  • DNA, Neoplasm
  • DNA, Viral
  • RASSF1 protein, human
  • Tumor Suppressor Proteins
  • UCHL1 protein, human
  • DAPK1 protein, human
  • Death-Associated Protein Kinases
  • Ubiquitin Thiolesterase