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Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma

胰腺导管癌患者胰液导管细胞特异激活基因的筛选

基本信息

批准号：
13670549
负责人：
MANO Hiroyuki
金额：
$ 2.3万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670549/
关键词：
Pancreatic carcinoma DNA chip

项目摘要

Pancreatic ductal carcinoma (PDC) is one of the most intractable human malignancies. Surgical resection of PDC at curable stages is hampered by a lack of sensitive and reliable detection methods. Given that DNA microarray analysis allows the expression of thousands of genes to be monitored simultaneously, it offers a potentially suitable approach to the identification of molecular markers for the clinical diagnosis of PDC. However, a simple comparison between the transcriptomes of normal and cancerous pancreatic tissue is likely to yield misleading pseudopositive data that reflect mainly the different cellular compositions of the specimens. **deed, a microarray comparison of normal and cancerous tissue identified the insulin gene as one of the genes whose expression *** most specific to normal tissue. To eliminate such a "population-shift" effect, the pancreatic ductal epithelial cells were purified by MUC1-based affinity chromatography from pancreatic juice isolated from both healthy individuals and PDC patients. Analysis of these background-matched samples with DNA microarrays representing 3456 human genes resulted in the identification of candidate genes for PDC-specific markers, including those for AC133 and carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7). Specific expression of these genes in the ductal cells of the patients with PDC was confirmed by quantitative real-time polymerase chain reaction analysis. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC that relies on pancreatic juice, which is routinely obtained in the clinical setting.

胰导管癌（Pancreatic ductal carcinoma， PDC）是人类最难治的恶性肿瘤之一。由于缺乏敏感可靠的检测方法，在可治愈期手术切除PDC受到了阻碍。鉴于DNA微阵列分析可以同时监测数千个基因的表达，它为PDC的临床诊断提供了一种潜在的合适的分子标记鉴定方法。然而，对正常和癌胰腺组织的转录组进行简单的比较很可能产生误导性的假阳性数据，这些数据主要反映了标本的不同细胞组成。事实上，通过对正常组织和癌变组织的微阵列比较发现，胰岛素基因是正常组织中表达最特异的基因之一。为了消除这种“群体转移”效应，采用基于muc1的亲和层析法从健康个体和PDC患者分离的胰腺液中纯化胰腺导管上皮细胞。用DNA微阵列分析这些背景匹配的样本，代表3456个人类基因，鉴定出pdc特异性标记的候选基因，包括AC133和癌胚抗原相关细胞粘附分子7 （CEACAM7）。这些基因在PDC患者导管细胞中的特异性表达通过实时定量聚合酶链反应分析得到证实。因此，纯化胰腺导管细胞的微阵列分析为开发一种依赖于临床常规获得的胰液检测PDC的灵敏方法提供了基础。