Frequent loss of RUNX3 gene expression in remnant stomach cancer and adjacent mucosa with special reference to topography
Frequent loss of RUNX3 gene expression in remnant stomach cancer and adjacent mucosa with special reference to topography
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DOI：
10.1038/sj.bjc.6602372
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发表时间：
2005-02-14
影响因子：
8.8
通讯作者：
Ito, Y
中科院分区：
文献类型：
--
作者：
Nakase, Y;Sakakura, C;Ito, Y
我们前期的研究表明RUNX 3功能的缺失与胃癌的发生和发展有因果关系。进行本研究以确定是否可以在外观正常的残胃粘膜中检测到RUNX 3基因表达的改变，并通过分析RUNX 3表达并特别参考地形图来确定在消化性溃疡（RB组）或胃癌（RM组）的远端胃切除术后，吻合部位与残胃中其他区域之间胃癌发生潜力的任何差异。共89例患者接受了完整胃的远端胃癌切除术（GCI组），58例患者接受了残胃胃癌切除术（RB组：34例，RM组：24例）。采用原位杂交、定量逆转录-聚合酶链反应（RT-PCR）和甲基化特异性PCR检测RUNX 3和基因启动子甲基化。RM组首次手术与残胃癌手术之间的间隔时间（间隔时间）为10.4年，RB组为27.5年。RB组的肿瘤以吻合口为主（P < 0.05）。在肿瘤内，三组中RUNX 3表达的下调范围为74.7%至85.7%。RUNX 3在RB组和RM组中的表达下调率分别为39.2%（11/28）和47.6%（10/21），显著高于GCI组（19.5%（17/87））。在RB组残胃的非癌粘膜中，RUNX 3表达在吻合口附近降低更多。然而，在RM组中，不同采样位置的RUNX 3表达没有显着差异。基于RUNX 3下调和临床特征，与RB或GCI组相比，RM组的残留胃粘膜具有更高的胃癌发生潜力。RB组残胃粘膜具有更高的电位，尤其是比残胃粘膜的其他区域。检测残胃粘膜中RUNX 3的表达和甲基化可能有助于预测残胃癌变的远期风险。
Our previous studies suggest that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer. This study was conducted to determine whether alteration of RUNX3 gene expression could be detected in the normal- looking gastric remnant mucosa, and to ascertain any difference in the potential of gastric carcinogenesis between the anastomotic site and other areas in the remnant stomach after distal gastrectomy for peptic ulcer ( RB group) or gastric cancer ( RM group), by analysing RUNX3 expression with special reference to topography. A total of 89 patients underwent distal gastrectomy for gastric cancer from the intact stomach ( GCI group) and 58 patients underwent resection of the remnant stomach for gastric cancer ( RB group: 34 cases, RM group: 24 cases). We detected RUNX3 and gene promoter methylation by in situ hybridisation, quantitative reverse transcriptase - polymerase chain reaction ( RT - PCR), and methylation- specific PCR. The interval between the initial surgery and surgery for remnant gastric cancer ( interval time) was 10.4 years in the RM group, and 27.5 years in the RB group. Cancers in the RB group were significantly more predominant in the anastomosis area ( P < 0.05). Within the tumour, downregulation of RUNX3 expression ranged from 74.7 to 85.7% in the three groups. The rate of downregulation of RUNX3 of adjacent mucosa was 39.2% ( 11 in 28 cases) in RB and 47.6% ( 10 in 21 cases) in RM, which are significantly higher than that of the GCI group ( 19.5%, 17 in 87 cases). In noncancerous mucosa of the remnant stomach in the RB group, RUNX3 expression decreased more near the anastomosis area. In the RM group, however, there were no significant differences in RUNX3 expression by sampling location. Based on RUNX3 downregulation and clinical features, residual stomach mucosa of the RM group would have a higher potential of gastric carcinogenesis compared to the RB or GCI group. Gastric stump mucosa of the RB group has higher potential especially than other areas of residual stomach mucosa. Measurement of RUNX3 expression and detection of RUNX3 methylation in remnant gastric mucosa may estimate the forward risk of carcinogenesis in the remnant stomach.