Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays
Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays
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DOI：
10.1016/s0002-9440(10)63911-9
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发表时间：
2003-04-01
影响因子：
6
通讯作者：
Goggins, M
中科院分区：
文献类型：
--
作者：
Iacobuzio-Donahue, CA;Maitra, A;Goggins, M
胰腺癌是美国癌症死亡的第五大原因。我们使用cDNA微阵列分析了14个胰腺癌细胞系、17个切除的浸润性胰腺癌组织和5个正常胰腺样品中的全局基因表达模式，以鉴定在胰腺癌中差异表达的基因。我们发现了400多个cDNA对应于与正常胰腺相比在胰腺癌组织和细胞系中差异表达的基因。这些在胰腺癌中倾向于以较高水平表达的基因与多种过程相关，包括细胞-细胞和细胞基质相互作用、细胞骨架重塑、蛋白水解活性和Ca++稳态。两个突出的基因簇与胰腺癌细胞系中的高细胞增殖率和切除的胰腺癌组织中的宿主促纤维增生反应有关。与正常胰腺相比，在胰腺癌中被鉴定为更高表达的149个基因中，有103个基因先前未被报道与胰腺癌相关。这些高表达基因中的14个的表达模式通过免疫组织化学或逆转录-聚合酶链反应被证实在胰腺癌中表达。一个基因的过度表达，特别是14-3-3sigma，被发现与大多数分析的胰腺癌中的异常低甲基化相关。本研究中的基因和表达序列标签为胰腺癌的病理生物学提供了线索，并为胰腺癌的检测和治疗提供了大量潜在的新分子标志物。
Pancreatic cancer is the fifth leading cause of cancer death in the United States. We used cDNA microarrays to analyze global gene expression patterns in 14 pancreatic cancer cell lines, 17 resected infiltrating pancreatic cancer tissues, and 5 samples of normal pancreas to identify genes that are differentially expressed in pancreatic cancer. We found more than 400 cDNAs corresponding to genes that were differentially expressed in the pancreatic cancer tissues and cell lines as compared to normal pancreas. These genes that tended to be expressed at higher levels in pancreatic cancers were associated with a variety of processes, including cell-cell and cell matrix interactions, cytoskeletal remodeling, proteolytic activity, and Ca++ homeostasis. Two prominent clusters of genes were related to the high rates of cellular proliferation in pancreatic cancer cell lines and the host desmoplastic response in the resected pancreatic cancer tissues. Of 149 genes identified as more highly expressed in the pancreatic cancers compared with normal pancreas, 103 genes have not been previously reported in association with pancreatic cancer. The expression patterns of 14 of these highly expressed genes were validated by either immunohistochemistry or reverse transcriptase-polymerase chain reaction as being expressed in pancreatic cancer. The overexpression of one gene in particular, 14-3-3sigma, was found to be associated with aberrant hypomethylation in the majority of pancreatic cancers analyzed. The genes and expressed sequence tags presented in this study provide clues to the pathobiology of pancreatic cancer and implicate a large number of potentially new molecular markers for the detection and treatment of pancreatic cancer.