A microarray-based gastric carcinoma prewarning system
A microarray-based gastric carcinoma prewarning system
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DOI：
10.3748/wjg.v11.i9.1273
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发表时间：
2005-03-07
影响因子：
4.3
通讯作者：
Gao, Hua-Jian
中科院分区：
文献类型：
--
作者：
Cui, Da-Xiang;Zhang, Li;Gao, Hua-Jian
目的：目的：建立一个由胃癌芯片、预警数据和分析软件组成的胃癌及癌前病变早期预警系统，方法：采用2个含有8464个人类cDNA位点的高密度芯片，初步筛选正常胃粘膜、癌前病变和胃癌的特异性基因。选取正常胃粘膜、癌前病变和胃癌相关基因，制作低密度芯片，对150例标本（胃癌60例，癌前组织60例，正常胃粘膜30例）进行筛选。应用CAD软件筛选出区分正常粘膜、癌前病变和癌的相关基因及其表达水平的临界阈值。所有数据存入计算机数据库，建立胃癌预警数据库。结果：共筛选出412个与胃癌发生、发展3个阶段相关的基因。胃癌组织中高表达基因216个，癌前病变中高表达基因85个，正常胃黏膜中高表达基因88个。筛选出15个与胃癌转移相关的基因和8个与胃癌危险因素相关的基因作为胃癌早期诊断芯片的靶基因。412个筛选基因区分胃癌、癌前病变和正常胃粘膜的阈值分别为6.01 ± 2.40、4.86 ± 1.94和5.42 ± 2.17。将这些选定的412个基因和临界阈值编译成分析软件，该软件可以通过分析通过检查胃组织获得的412个基因的结果来自动提供报告。所有数据经CGO软件编制成胃癌预警数据库。北方杂交和免疫组化分析证实，brcaa1基因和蛋白在正常胃粘膜中呈低表达，在胃癌组织中呈高表达，而ndr 1基因和蛋白在胃癌组织中呈低表达，在正常胃粘膜中呈高表达。该系统由胃癌相关基因芯片、预警数据和分析软件组成，在胃癌的早期检测中具有很大的应用潜力。所鉴定的两个潜在标记物brcaa1和ndr 1可用于区分癌症状态和非癌症状态。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To develop a microarray-based prewarning system consisting of gastric cancer chip, prewarning data and analysis software for early detection of gastric cancer and pre-cancerous lesions.METHODS: Two high-density chips with 8 464 human cDNA sites were used to primarily identify potential genes specific for normal gastric mucosa, pre-cancerous lesion and gastric cancer. The low-density chips, composed of selected genes associated with normal gastric mucosa, precancerous lesion and gastric cancer, were fabricated and used to screen 150 specimens including 60 specimens of gastric cancer, 60 of pre-cancerous tissues and 30 of normal gastric mucosa. CAD software was used to screen out the relevant genes and their critical threshold values of expression levels distinguishing normal mucosa from pre-cancerous lesion and cancer. All data were stored in a computer database to establish a prewarning data library for gastric cancer. Two potential markers brcaa1 and ndr1 were identified by Western blot and immunohistochemistry.RESULTS: A total of 412 genes associated with three stages of gastric cancer development were identified. There were 216 genes displaying higher expression in gastric cancer, 85 genes displaying higher expression in pre-cancerous lesion and 88 genes displaying higher expression in normal gastric mucosa. Also 15 genes associated with metastasis of gastric cancer and 8 genes associated with risk factors were screened out for target genes of diagnosis chip of early gastric cancer. The threshold values of 412 selected genes to distinguish gastric cancer, pre-cancerous lesion from normal gastric mucosa were defined as 6.01 +/- 2.40, 4.86 +/- 1.94 and 5.42 +/- 2.17, respectively. These selected 412 genes and critical threshold values were compiled into an analysis software, which can automatically provide reports by analyzing the results of 412 genes obtained by examining gastric tissues. All data were compiled into a prewarning database for gastric cancer by CGO software. Northern blot and immunohistochemistry analysis confirmed that gene and protein of brcaa1 displayed lower expression in normal gastric mucosa and higher expression in gastric cancer tissues, conversely, ndr1 displayed lower expression in gastric cancer and higher expression in normal gastric mucosa.CONCLUSION: The microarray-based prewarning system for gastric cancer was developed. This system consisted of gastric cancer-associated gene chip, prewarning data and analysis software, which has a high potential for applications in the early detection of gastric cancer. The two potential markers brcaa1 and ndr1 identified may be used to distinguish cancer status fand non-cancer status. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.