胃癌与慢性萎缩性胃炎基因表达谱的差异和关联

The difference and relationship of gene expression profiles between gastric cancer and chronic atrophic gastritis

背景与目的:胃黏膜自慢性炎症演变为胃癌的过程中,隐伏着一系列的基因变化。本研究采用高通量基因芯片,检测慢性萎缩性胃炎和胃癌组织的基因表达,结合病理资料,分析和比较两者基因表达的异常及其生物学意义。方法:收集23例胃癌以及15例慢性萎缩性胃炎的病变及配对非病变部位胃粘膜组织,以载有13824个基因/EST序列的基因芯片检测基因表达谱,结合病理等临床资料,应用系统聚类法、t检验、Fisher确切概率法等统计学方法进行分析。结果:胃癌组和慢性萎缩性胃炎组分别筛选出符合条件的基因53个和21个。胃癌组的特征性表达基因中,STS、HAP1等基因与Borrmann分型等病理改变相关联;慢性萎缩性胃炎组的特征性表达基因中,BRD3、BF508879等基因与肠化等病理改变相关联;慢性萎缩性胃炎和胃癌组中共同存在的SLC26A3等基因与癌前病变相关联。结论:慢性萎缩性胃炎和胃癌组织基因的表达既有相似性,又有异质性。肿瘤基因表达与癌前状态和癌前病变相关。基因表达的相似性提示慢性萎缩性胃炎与胃癌这两者病理发展的相关性和延续性。

Background and purpose： The development of gastric cancer has a long course from chronic mucosal inflammation and involves a lot of genes. We investigated the different gene expression profiles with gene chip of high flux between gastric cancer and chronic atrophic gastritis so as to analyze their biologic significance, combined with endoscopic findings and surgical pathology. Methods： Paired pathological and non-pathological specimens from 23 patients with gastric cancer and 15 with chronic atrophic gastritis were enrolled for the study. Gene chip with 13 824 genes/ESTs was employed for detection of the expression profile, while endoscopic and pathologic findings were collected for evaluation. Data were analyzed by average-linkage hierarchical clustering, t test and Fisher calculation of exact probability. Results： Fifty-three specific genes were filtered from gastric cancer group, and 21 from chronic atrophic gastritis group. In the former group, STS, HAP1 and some other relatively specific genes were expressed in correlation to the Borrmann＇ s classification, while in the latter group, BRD3 and BF508879 were demonstrated positively in correlation to intestinal metaplasia. However, there were also some specific genes, such as SLC26A3, related to precancerous condition, commonly expressed in both two groups. Conclusions： There was either homogenous or heterogeneous gene expression profile in gastric cancer as well as in chronic atrophic gastritis. Abnormal gene expressions were related to precancerous conditions or precancerous lesions and to biologic behavior of tumor. The difference and comparability of gene expression in the two groups studied shows the continuity and pertinence of the two diseases.