Eradication of H. pylori did not improve abnormal sonic hedgehog expression in the high risk group for gastric cancer

Dig Dis Sci. 2012 Mar;57(3):643-9. doi: 10.1007/s10620-011-1916-3. Epub 2011 Sep 28.


Background: Sonic hedgehog (SHH) acts as a proliferation factor in both the normal mucosa and in malignant lesions. Helicobacter pylori-associated atrophic gastritis is characterized by loss of SHH.

Aim: The purpose of this study was to investigate the effects of H. pylori eradication on SHH mRNA and methylation levels in the patients at high risk for gastric cancer comparing to those in the controls.

Methods: Gastric corpus biopsies taken from 20 patients with endoscopic resection for early gastric cancer and 14 sex- and age-matched controls before and 1 year after eradication were examined for SHH and downstream regulators mRNA expression using whole biopsy specimens and microdissected gastric glands. Methylation of SHH promoter was evaluated using quantitative methylation-specific PCR.

Results: SHH mRNA levels eradication were significantly lower (2.75 × 10(-2) vs. 7.37 × 10(-2), P = 0.004) in the cancer group than in the controls. PTCH and BMP4 mRNA levels as well as MUC5AC were significantly increased only in the control group and were significantly higher in the controls than those in the cancer group after eradication. After eradication, SHH methylation levels in the non-metaplastic glands were significantly higher (86.4% vs. 22.2%, P < 0.001) in the cancer group than in the controls.

Conclusions: H. pylori eradication can enhance SHH and its downstream regulators expression diminishing SHH methylation and reverse gastric phenotype, but not in the patients with high risk for gastric cancer.

MeSH terms

  • Aged
  • Biopsy
  • Bone Morphogenetic Protein 4 / genetics
  • Case-Control Studies
  • DNA Methylation / genetics
  • Female
  • Gastric Mucosa / pathology
  • Gastric Mucosa / physiology
  • Gastritis, Atrophic / epidemiology*
  • Gastritis, Atrophic / genetics
  • Gastritis, Atrophic / pathology
  • Genetic Predisposition to Disease / epidemiology
  • Hedgehog Proteins / genetics*
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / epidemiology*
  • Helicobacter pylori*
  • Humans
  • Male
  • Middle Aged
  • Mucin 5AC / genetics
  • Patched Receptors
  • Patched-1 Receptor
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Receptors, Cell Surface / genetics
  • Risk Factors
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics
  • Zinc Finger Protein GLI1


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • GLI1 protein, human
  • Hedgehog Proteins
  • MUC5AC protein, human
  • Mucin 5AC
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface
  • SHH protein, human
  • Transcription Factors
  • Zinc Finger Protein GLI1