Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma
Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma
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DOI：
10.1038/modpathol.3800337
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发表时间：
2005-06-01
期刊：
影响因子：
7.5
通讯作者：
Goggins, M
中科院分区：
文献类型：
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作者：
Fukushima, N;Koopmann, J;Goggins, M
浸润性导管腺癌旁的非肿瘤性胰腺实质表现为炎症、纤维化、腺泡细胞丢失和腺泡细胞的小管样化生。在慢性胰腺炎的情况下也观察到类似的形态学变化。此外，肿瘤周围腺泡已被证明有基因表达的改变，即使在没有形态学变化。为了更好地了解胰腺腺泡对浸润性胰腺导管腺癌的反应，我们描述了浸润性胰腺导管腺癌附近胰腺腺泡组织的基因表达模式，并将其与慢性胰腺炎影响的腺泡组织以及正常胰腺腺泡的基因表达模式进行了比较。新鲜冷冻的胰腺腺泡组织从9例患者（3例胰腺癌，3例慢性胰腺炎，3例正常胰腺），使用激光捕获显微切割，从每个显微切割提取的RNA进行两轮线性扩增和杂交寡核苷酸微阵列。使用定量RT-PCR和/或免疫组织化学确认基因表达模式。与正常腺泡组织和受慢性胰腺炎影响的腺泡相比，共发现20个基因在瘤周腺泡组织中过表达。这20个基因包括胰腺炎相关蛋白（HIP/PAP），一种已知在浸润性胰腺癌附近腺泡中过表达的基因，以及软骨糖蛋白-39（HC gp-39或TKL-40）基因。胰腺癌患者和慢性胰腺炎患者的血清HC gp-39蛋白水平显著高于无胰腺疾病的对照组。胰腺癌患者与慢性胰腺炎患者血清HC gp-39水平无显著性差异。我们的研究结果表明，在腺泡细胞中发生的一些分子改变，在响应相邻的浸润性胰腺导管腺癌，并揭示这种改变可以提供一个丰富的来源胰腺癌的标志物。
The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients ( three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.