应用基因芯片技术筛查肠型胃癌发生发展中差异基因表达的研究

Screening for differential gene expression in the development of intestinal-type gastric cancer

目的应用寡核苷酸芯片研究胃正常组织、慢性萎缩性胃炎伴肠上皮化生、慢性萎缩性胃炎伴非典型性增生和肠型胃癌黏膜的基因表达谱,筛选肠型胃癌发生相关基因。方法利用激光切割显微捕获联合基因芯片研究胃正常黏膜组织与慢性萎缩性胃炎伴肠上皮化生、慢性萎缩性胃炎伴非典型性增生和肠型胃癌黏膜组织研究肠型胃癌发展中的差异基因表达谱。结果在慢性萎缩性胃炎伴肠上皮化生、慢性萎缩性胃炎伴非典型性增生和肠型胃癌黏膜组织中,筛选出共同差异基因109个,其中有61个基因持续上调表达,48个基因持续下调表达,包括细胞信号传导、细胞周期相关基因、代谢酶类相关基因、细胞信号和传递蛋白、细胞外基质基因、原癌基因、抑癌基因、细胞黏附分子、生长因子、免疫相关基因、细胞骨架和运动相关蛋白、凋亡相关基因和肿瘤相关抗原等。将各组筛选出的基因进行聚类并结合各组临床病理资料统计分析后发现一些表达上具有特征意义的基因。其中ALDOB下调、CDX2和MUC2上调与Hp感染和肠化之间存在关联;Bim-1、hTERT、PTTG和COX2上调,TFF3下调与肠上皮化生和不典型增生具有相关性;Bim-1、PGA5、HAP1、STS和LIPF表达改变与胃癌Borrmann分型、Hp感染阳性率和淋巴结转移数目等存在关联;在慢性萎缩性胃炎伴肠上皮化生、慢性萎缩性胃炎伴非典型性增生和肠型胃癌黏膜共同差异基因中聚类分析并结合临床资料分析发现,ALDOB和TFF3表达下调与肠上皮化生具有负相关性,hTERT、COX-2和hMSH2上调和上皮非典型增生具有正相关。结论基因表达谱芯片能够快速筛选出肠型胃癌发生癌相关基因,有多种基因共同参与肠型胃癌发生的整个过程。

[Objectives] To screen differential expression gene of normal gastric mucosa, chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia and intestinal type gastric cancer expression by using oligonucleotide chip. [Methods] Normal gastric mucosa, chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia and intestinal type gastric were used to screen differential expression gene. [Results] 109 differential expression genes were found among normal gastric mueosa and atrophic gastritis, intestinal metaplasia, dysplasia and intestinal type gastric carcinoma, 61 of which showed continued increase expression, 48 of them showed to continued decrease expression. These genes including cell signal transduction and cell cycle-related genes, metabolic enzyme-related genes, cell signal and transmission of proteins, extracellular matrix genes, proto-oncogenes, tumor suppressor genes, cell adhesion molecules, growth factors, immune-related genes, and sports-related cytoskeletal protein, apoptosis-related genes, such as tumor-associated antigen. Downregulation of ALDOB,and increase expression of CDX2 and MUC2 have good correlation with Hp infection and the existence of intestinal metaplasia; the expression of Bim-1, hTERT, FFFG, COX2 and TFF3 have good correlation with intestinal metaplasia and dysplasia. The expression of Bim-1, PGA5, HAP1, STS and LIPF have good correlation with Borrmann type, Hp, infection and the number of lymph node metastasis; in patients with chronic atrophic gastritis with intestinal metaplasia, chronic atrophic gastritis with intestinal type of atypical hyperplasia and gastric cancer mucosa of the common differential gene cluster analysis in combination with clinical data analysis, downexpression of ALDOB and TFF3 have negative associated with intestinal metaplasia, increases expression of hTERT, COX-2 and hMSH2 have positive correlation with epithelial dysplasia. [Conclusion] cDNA microarray can quickly screen the differential expression gene in the development and progression of intestinal type gastric, there are several genes involved in common type the entire process of gastric cancer.