Methylation of DAPK and THBS1 genes in esophageal gastric-type columnar metaplasia

World J Gastroenterol. 2016 May 14;22(18):4567-75. doi: 10.3748/wjg.v22.i18.4567.

Abstract

Aim: To explore methylation of DAPK, THBS1, CDH-1, and p14 genes, and Helicobacter pylori (H. pylori) status in individuals harboring esophageal columnar metaplasia.

Methods: Distal esophageal mucosal samples obtained by endoscopy and histologically diagnosed as gastric-type (non-specialized) columnar metaplasia, were studied thoroughly. DNA was extracted from paraffin blocks, and methylation status of death-associated protein kinase (DAPK), thrombospondin-1 (THBS1), cadherin-1 (CDH1), and p14 genes, was examined using a methyl-sensitive polymerase chain reaction (MS-PCR) and sodium bisulfite modification protocol. H. pylori cagA status was determined by PCR.

Results: In total, 68 subjects (33 females and 35 males), with a mean age of 52 years, were included. H. pylori cagA positive was present in the esophageal gastric-type metaplastic mucosa of 18 individuals. DAPK, THSB1, CDH1, and p14 gene promoters were methylated by MS-PCR in 40 (58.8%), 33 (48.5%), 46 (67.6%), and 23 (33.8%) cases of the 68 esophageal samples. H. pylori status was associated with methylation of DAPK (P = 0.003) and THBS1 (P = 0.019).

Conclusion: DNA methylation occurs in cases of gastric-type (non-specialized) columnar metaplasia of the esophagus, and this modification is associated with H. pylori cagA positive infection.

Keywords: DNA methylation; Death-associated protein kinase; Esophageal columnar metaplasia; Helicobacter pylori; Thrombospondin-1; cagA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Bacterial / genetics
  • Antigens, CD
  • Bacterial Proteins / genetics
  • Biomarkers, Tumor / genetics*
  • Cadherins / genetics
  • DNA Methylation*
  • Death-Associated Protein Kinases / genetics*
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / microbiology
  • Esophageal Neoplasms / pathology
  • Female
  • Helicobacter pylori / genetics
  • Humans
  • Male
  • Mexico
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Thrombospondin 1 / genetics*
  • Tumor Suppressor Protein p14ARF / genetics

Substances

  • Antigens, Bacterial
  • Antigens, CD
  • Bacterial Proteins
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Thrombospondin 1
  • Tumor Suppressor Protein p14ARF
  • cagA protein, Helicobacter pylori
  • thrombospondin-1, human
  • Death-Associated Protein Kinases