Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama Prefecture 01-0192, Japan.
Dig Dis Sci. 2012 Mar;57(3):643-9. doi: 10.1007/s10620-011-1916-3. Epub 2011 Sep 28.
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.
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.
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.
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.
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.
Sonic hedgehog(SHH)在正常黏膜和恶性病变中均作为增殖因子发挥作用。幽门螺杆菌相关性萎缩性胃炎的特征是 SHH 丧失。
本研究旨在探讨与对照组相比,根除幽门螺杆菌对胃癌高危患者胃黏膜 SHH mRNA 和甲基化水平的影响。
对 20 例接受早期胃癌内镜切除术的患者和 14 例性别和年龄匹配的对照者的胃体活检标本进行了研究,在根除前和根除后 1 年,采用全活检标本和微切割胃腺,检测 SHH 和下游调节因子 mRNA 的表达。采用定量甲基化特异性 PCR 评估 SHH 启动子的甲基化。
与对照组相比,癌症组的 SHH mRNA 水平(2.75×10(-2) vs. 7.37×10(-2),P=0.004)在根除后显著降低。PTCH 和 BMP4 mRNA 水平以及 MUC5AC 仅在对照组中显著增加,且在根除后对照组高于癌症组。根除后,非化生腺中的 SHH 甲基化水平在癌症组中(86.4% vs. 22.2%,P<0.001)显著高于对照组。
根除幽门螺杆菌可增强 SHH 及其下游调节因子的表达,降低 SHH 甲基化,逆转胃表型,但在胃癌高危患者中并非如此。