Kim Kyong Rae, Oh Soo Youn, Park Ung Chae, Wang Joon Ho, Lee Jae Dong, Kweon Hyuk Jung, Kim Sang Yoon, Park Seung Hwa, Choi Dong Kug, Kim Chan Gil, Choi Seongc Ho
Department of General Surgery, Konkuk University College of Medicine, Chungju, Korea.
Korean J Gastroenterol. 2007 Apr;49(4):209-24.
BACKGROUND/AIMS: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach.
We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization.
Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern.
We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.
背景/目的:胃黏膜萎缩性胃炎伴肠化生被认为是胃癌发生的主要因素。然而,关键分子仍未完全清楚。为阐明分子遗传学基础,我们报告了初步的微阵列数据结果,以分析萎缩性胃炎和胃肠化生患者的基因组模式。
我们使用寡核苷酸微阵列技术评估萎缩性胃炎伴肠化生患者的基因表达谱,并与正常黏膜的基因表达谱进行比较。采用微阵列显著性分析(SAM)软件包方法鉴定差异表达基因。结果采用全局归一化、强度依赖归一化和箱线图归一化进行分析。
与正常胃黏膜相比,萎缩性胃炎和肠化生黏膜中的8个基因,包括脂肪酸结合蛋白(FABP)、再生基因(REG)、嗅觉受体6C1(OR6C1)、金属肽酶1(MEP1)、溶质载体家族6成员1(SLC6A1)、唾液淀粉酶(SI)、黏蛋白1和RAB23基因上调超过10倍。只有一个基因,即LOC44119,与正常胃黏膜相比表达下调超过10倍。关于与胃癌发生相关的已知基因的表达,包括纤连蛋白1(FN1)、Src相关的肌肉特异性蛋白(SRMS)、肿瘤蛋白p53(TP53)、TP53相互作用分子2(TP53IMP2)、TP53诱导蛋白3(TP53I3)、成纤维细胞生长因子受体4(FGFR4)、转化生长因子β1(TGFB1)和转化生长因子α(TGFA)在内的8个基因在表达模式上有超过2倍的上调和下调。
我们使用寡核苷酸微阵列能够鉴定萎缩性胃炎和肠化生患者的全基因组模式。我们相信,目前的结果将为未来胃癌及癌前病变的诊断和治疗临床应用提供一个基本的生物信息学基础。