Xu Wen-jie, Zhou Jian-jiang, Xie Yuan, Wang Wen-ling, Zhao Yan, Chen Xian, Li Yi
Guiyang Medical University, Guiyang, China.
Zhonghua Yi Xue Za Zhi. 2012 Feb 14;92(6):366-70.
To explore the association between the Helicobacter pylori (H. pylori) infection and the expression and methylation of energy-related genes in gastric cancer.
Real-time fluorescence quantitative reverse transcription (RT)-PCR was performed to quantify the expressions level of lactate dehydrogenase (LDH), dihydrolipoamide dehydrogenase (DLD) and Ran-specific GTPase-activating protein (RanGAP) genes in the samples of human gastric cancer (n = 30), metastatic lymph node (n = 30) and peri-cancerous tissues (n = 30) as confirmed by pathological examinations. Those patients were chosen of Affiliated Hospital of Guiyang Medical University, from January 2005 to December 2009. The relationship between the gene expression and H. pylori infection was analyzed. The methylation of LDH, DLD and RanGAP genes at promoter CpG island was measured by bisulfite sequencing (BSP).
The relative gene expressions of LDH, DLD and RanGAP in peri-cancerous tissues, gastric cancer and metastatic lymph nodes were 1.0, 3.1, 3.0 and 1.0, 3.1, 2.8, and 1.0, 0.4, 0.5 respectively (all P < 0.05). The expression levels of LDH and DLD genes in H. pylori-positive gastric cancer was high than those in the negative group (2.3 vs 1.0, 3.0 vs 1.0, 2.6 vs 1.0, all P < 0.05). The demethylation of LDH and DLD genes at promoter -2325 and -1885 site as well as the over methylation of RanGAP gene at the promoter -570 and -170 sites respectively were detected in H. pylori infection and cagA-overexpressed cells.
H. pylori infection may promote the development and progression of gastric cancer by inducing the aberrant methylation of LDH, DLD and RanGAP genes to up-regulate the gene expressions of LDH and DLD and down-regulate the gene expression of RanGAP.
探讨幽门螺杆菌（H. pylori）感染与胃癌中能量相关基因的表达及甲基化之间的关联。
采用实时荧光定量逆转录（RT）-PCR对经病理检查确诊的人胃癌组织（n = 30）、转移淋巴结组织（n = 30）及癌旁组织（n = 30）中乳酸脱氢酶（LDH）、二氢硫辛酰胺脱氢酶（DLD）和Ran特异性GTP酶激活蛋白（RanGAP）基因的表达水平进行定量分析。这些患者选自贵阳医学院附属医院2005年1月至2009年12月期间的病例。分析基因表达与H. pylori感染之间的关系。通过亚硫酸氢盐测序（BSP）检测LDH、DLD和RanGAP基因启动子CpG岛的甲基化情况。
癌旁组织、胃癌组织及转移淋巴结中LDH、DLD和RanGAP的相对基因表达分别为1.0、3.1、3.0；1.0、3.1、2.8；1.0、0.4、0.5（均P < 0.05）。H. pylori阳性胃癌中LDH和DLD基因的表达水平高于阴性组（2.3 vs 1.0、3.0 vs 1.0、2.6 vs 1.0，均P < 0.05）。在H. pylori感染及cagA过表达细胞中，分别检测到LDH和DLD基因启动子-2325和-1885位点的去甲基化以及RanGAP基因启动子-570和-170位点的过甲基化。
H. pylori感染可能通过诱导LDH、DLD和RanGAP基因的异常甲基化，上调LDH和DLD的基因表达，下调RanGAP的基因表达，从而促进胃癌的发生发展。
