Evaluation of a biomarker for the diagnosis of pancreas cancer using an animal model
Evaluation of a biomarker for the diagnosis of pancreas cancer using an animal model
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DOI：
10.1293/tox.2018-0062
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发表时间：
2019-01-01
影响因子：
1.2
通讯作者：
Suzui, Masumi
中科院分区：
文献类型：
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作者：
Fukamachi, Katsumi;Hagiwara, Yoshiaki;Suzui, Masumi
人们已经采取了许多方法来鉴定胰腺导管癌（PDC）的新生物标志物。由于动物模型可以在受控条件下采样，因此与异质人类研究相比，可以实现更好的标准化。胰腺组织中致癌 RAS 条件性激活的转基因大鼠产生的 PDC 与人类 PDC 的生物学和组织病理学特征非常相似。使用该模型，我们评估了富含亮氨酸的 α 2-糖蛋白-1 (LRG-1) 作为血清标记物的有用性。在这项研究中，我们发现与对照大鼠的正常胰腺组织相比，LRG-1在大鼠PDC中过度表达。携带 PDC 的大鼠中 LRG-1 的血清水平也显着高于对照组。重要的是，雄性 Wistar Bonn/Kobori 大鼠的慢性胰腺炎（被广泛接受为慢性胰腺炎模型）不会导致 LRG-1 血清水平升高。这些结果有力地支持血清LRG-1作为PDC无创诊断的候选生物标志物。我们的胰腺癌模型为评估适用于人类癌症的候选标记物提供了有用的策略。
Many approaches have been taken to identify new biomarkers of pancreatic ductal carcinoma (PDC). Since animal models can be sampled under controlled conditions, better standardization is possible compared with heterogeneous human studies. Transgenic rats with conditional activation of oncogenic RAS in pancreatic tissue develop PDC that closely resembles the biological and histopathological features of human PDC. Using this model, we evaluated the usefulness of leucine-rich alpha 2-glycoprotein-1 (LRG-1) as a serum marker. In this study, we found that LRG-1 was overexpressed in rat PDC compared with normal pancreas tissue of the control rats. Serum levels of LRG-1 were also significantly higher in rats bearing PDC than in controls. Importantly, chronic pancreatitis in male Wistar Bonn/Kobori rats, which is a widely accepted as a model of chronic pancreatitis, did not cause serum levels of LRG-1 to become elevated. These results strongly support serum LRG-1 as a candidate biomarker for noninvasive diagnosis of PDC. Our models of pancreas cancer provide a useful strategy for evaluation of candidate markers applicable to human cancer.