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[利用cDNA微阵列和聚类分析人腺癌的基因表达谱]

[Gene expression profile of human adenocarcinoma by cDNA microarray and clustering].

作者信息

Shao Yong, Yang Shao-bo, Wang Meng-wei, Wu Ben-yan, You Wei-di, Li Hong

机构信息

Department of Elderly Gastroenterology, General Hospital of Chinese PLA, Beijing, 100853 PR China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 Apr;21(2):110-5.

PMID:15079790
Abstract

OBJECTIVE

To investigate the gene expression profile of human gastric adenocarcinoma by means of cDNA microarray and to analyze its biological significance.

METHODS

Paired tumor and non-tumor specimens from 18 cases of advanced gastric adenocarcinoma were studied. Total RNA was isolated and labeled by reverse transcription reaction with cy5 and cy3 for cDNA probe. cDNA microarrays containing 148 genes were hybridized with labeled cDNA probe. Data from cDNA microarray experiments were analyzed by average-linkage hierarchical clustering and significance analysis of microarrays (SAM).

RESULTS

Eighteen tumor and non-tumor specimens were clearly divided by clustering analysis. Three features of gene expression profile were found in gastric adenocarcinoma and non-tumor tissues. The profile of differential gene expression in tumor and non-tumor tissues was mainly shown in feature B and feature C. In gastric adenocarcinoma tissues, the expression of genes in feature B was lower and that in feature C was higher. The profile of differential gene expression among gastric adenocarcinoma tissues was found in feature A. In feature A, the profile of similar gene expression was found in paired tumor and non-tumor tissues from 13 patients. SAM analysis showed that 19 genes in feature B and 12 genes in feature C were of significant difference between tumor and non-tumor specimens. The expression levels of genes related to cell cycle, growth factor, cell adhesion, and matrix remodeling were higher or lower in gastric adenocarcinoma tissues.

CONCLUSION

Data from cDNA microarray experiments can clearly distinguish gastric adenocarcinoma from non-tumor tissues. The profiles show that gene expression in gastric adenocarcinomas is both homogeneous and heterogeneous. The homogeneous gene expression profile is found in both tumor and non-tumor tissues from 13 patients, suggesting that some gene aberrance is an early event of carcinogenesis of gastric adenocarcinoma. This study provides not only a new molecular basis for understanding biological properties of gastric adenocarcinoma, but also useful resources for future development of diagnostic and prognostic markers for gastric adenocarcinoma.

摘要

目的

通过cDNA微阵列研究人胃腺癌的基因表达谱,并分析其生物学意义。

方法

研究18例进展期胃腺癌患者的肿瘤与非肿瘤配对标本。提取总RNA,通过逆转录反应分别用cy5和cy3标记,制成cDNA探针。将包含148个基因的cDNA微阵列与标记的cDNA探针进行杂交。采用平均连锁层次聚类和微阵列显著性分析(SAM)对cDNA微阵列实验数据进行分析。

结果

聚类分析可清晰区分18个肿瘤和非肿瘤标本。在胃腺癌和非肿瘤组织中发现了基因表达谱的三个特征。肿瘤与非肿瘤组织中差异基因表达谱主要体现在特征B和特征C中。在胃腺癌组织中,特征B中的基因表达较低,特征C中的基因表达较高。胃腺癌组织间差异基因表达谱存在于特征A中。在特征A中,13例患者的配对肿瘤和非肿瘤组织中发现了相似的基因表达谱。SAM分析显示,特征B中的19个基因和特征C中的12个基因在肿瘤与非肿瘤标本之间存在显著差异。与细胞周期、生长因子、细胞黏附及基质重塑相关的基因在胃腺癌组织中的表达水平有高有低。

结论

cDNA微阵列实验数据能清晰区分胃腺癌与非肿瘤组织。这些图谱表明胃腺癌中的基因表达既有同质性又有异质性。在13例患者的肿瘤和非肿瘤组织中均发现了同质性基因表达谱,提示某些基因异常是胃腺癌发生的早期事件。本研究不仅为理解胃腺癌的生物学特性提供了新的分子基础,也为未来胃腺癌诊断和预后标志物的开发提供了有用资源。

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