Kitajima Yoshihiko, Ohtaka Kazuma, Mitsuno Mayumi, Tanaka Masayuki, Sato Seiji, Nakafusa Yuji, Miyazaki Kohji
Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan.
Oncol Rep. 2008 Jan;19(1):197-202.
Runx3, a member of the human runt-related transcription factor family, is known as a possible tumor suppressor gene for gastric cancer. Runx 3 expression is frequently suppressed by the promoter hypermethylation in gastric cancer cell lines and tissues. However, the precise mechanism of the induction of Runx3 methylation, which is considered to be a critical step in gastric carcinogenesis, remains to be elucidated. In the present study, we evaluated runx3 gene methylation in 57 resected early gastric cancer specimens. Then, we correlated Runx3 methylation in the cancer tissue specimens with clinicopathological factors as well as the mucosal backgrounds, such as intestinal metaplasia surrounding the cancer cells and Helicobacter pylori (H. pylori) infection. Runx3 methylation was observed in 30 of the 57 (52.6%) cancer specimens, whereas methylation was detected in 10 of the 57 (17.5%) corresponding non-cancerous mucosae. In comparison to the clinicopathological factors, Runx3 methylation was significantly correlated with both age and tumor location. A multivariate analysis demonstrated that age and tumor location as well as H. pylori infection were independent risk factors for Runx3 methylation. We demonstrated for the first time that H. pylori infection contributes to Runx3 methylation in gastric cancer tissues. When a persistent infection by H. pylori continues in the middle/lower stomach for a long period, Runx3 methylation may be induced and the subsequent loss of Runx3 expression may therefore affect gastric carcinogenesis.
Runx3是人类与 runt 相关转录因子家族的成员之一，被认为是一种可能的胃癌抑癌基因。在胃癌细胞系和组织中，Runx3 的表达常常因启动子高甲基化而受到抑制。然而，Runx3 甲基化诱导的确切机制（这被认为是胃癌发生的关键步骤）仍有待阐明。在本研究中，我们评估了 57 例切除的早期胃癌标本中的 runx3 基因甲基化情况。然后，我们将癌组织标本中的 Runx3 甲基化与临床病理因素以及黏膜背景相关联，如癌细胞周围的肠化生和幽门螺杆菌（H. pylori）感染。在 57 例癌标本中有 30 例（52.6%）观察到 Runx3 甲基化，而在 57 例相应的非癌黏膜中有 10 例（17.5%）检测到甲基化。与临床病理因素相比，Runx3 甲基化与年龄和肿瘤位置均显著相关。多变量分析表明，年龄、肿瘤位置以及 H. pylori 感染是 Runx3 甲基化的独立危险因素。我们首次证明 H. pylori 感染会导致胃癌组织中的 Runx3 甲基化。当幽门螺杆菌在胃中下部持续长期感染时，可能会诱导 Runx3 甲基化，随后 Runx3 表达的丧失可能会影响胃癌的发生。
