Gene expression profiles of microdissected pancreatic ductal adenocarcinoma
Gene expression profiles of microdissected pancreatic ductal adenocarcinoma
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DOI：
10.1007/s00428-003-0884-1
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发表时间：
2003-10-01
期刊：
影响因子：
3.5
通讯作者：
Pilarsky, C
中科院分区：
文献类型：
--
作者：
Grützmann, R;Foerder, M;Pilarsky, C
在寻找胰腺导管腺癌（PDAC）的新分子标志物的过程中，我们比较了7个胰腺癌和1个乳头状乳头癌的基因表达谱与3个非肿瘤性胰腺组织的导管细胞的基因表达谱。此外，检查了人胰管细胞系和五种PDAC细胞系（AsPC-1、BxPC-3、Capan-1、Capan-2、HPAF）。从显微解剖的组织或培养的细胞系中提取RNA，并使用含有3023个基因的定制的Affytek芯片进行分析，其中1000个已知与肿瘤相关。聚类分析显示81个差异表达基因。在所有基因中，26个在PDAC中下调，14个在PDAC中上调。在PDAC细胞系与正常胰管细胞中，21个基因下调，20个基因上调。在这81个差异表达基因中，15个代表了先前与PDAC肿瘤发生有关的人类基因。从迄今为止尚不知道与PDAC肿瘤发生相关的基因中，我们选择了ADAM 9进行进一步验证，因为它在肿瘤组织中有明显的过表达。使用免疫组织化学，过表达的基因，ADAM 9，存在于70%的PDAC分析。总之，使用微阵列技术，我们能够识别一组基因，其异常表达与PDAC相关，并可用于靶向疾病。
In a search for new molecular markers of pancreatic ductal adenocarcinoma (PDAC), we compared the gene expression profiles of seven pancreatic carcinomas and one carcinoma of the papilla Vateri with those of duct cells from three non-neoplastic pancreatic tissues. In addition, the human pancreatic duct cell line and five PDAC cell lines (AsPC-1, BxPC-3, Capan-1, Capan-2, HPAF) were examined. RNA was extracted from microdissected tissue or cultured cell lines and analysed using a custom-made Affymetrix Chip containing 3023 genes, of which 1000 were known to be tumour associated. Hierarchical clustering revealed 81 differentially expressed genes. Of all the genes, 26 were downregulated in PDAC and 14 were upregulated in PDAC. In PDAC cell lines versus normal pancreatic duct cells, 21 genes were downregulated and 20 were upregulated. Of these 81 differentially expressed genes, 15 represented human genes previously implicated in the tumourigenesis of PDAC. From the genes that were so far not known to be associated with PDAC tumorigenesis, we selected ADAM9 for further validation because of its distinct overexpression in tumour tissue. Using immunohistochemistry, the over-expressed gene, ADAM9, was present in 70% of the PDACs analysed. In conclusion, using microarray technology we were able to identify a set of genes whose aberrant expression was associated with PDAC and may be used to target the disease.