Eradication ofH. pyloriDid Not Improve Abnormal Sonic Hedgehog Expression in the High Risk Group for Gastric Cancer

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Abstract

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 methylationspecific 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 nonmetaplastic 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.

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