Reduced α-Dystroglycan Expression Correlates with Shortened Patient Survival in Pancreatic Cancer
Reduced α-Dystroglycan Expression Correlates with Shortened Patient Survival in Pancreatic Cancer
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DOI：
10.1016/j.jss.2009.11.730
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发表时间：
2011-11-01
影响因子：
2.2
通讯作者：
Kleeff, Joerg
中科院分区：
文献类型：
--
作者：
Jiang, Xiaohua;Rieder, Simon;Kleeff, Joerg
背景。细胞-基质相互作用的解除被认为是恶性转化的重要因素。糖歧义蛋白通过α -糖歧义蛋白和β -糖歧义蛋白这两个亚基在上皮细胞的基底膜和细胞膜之间形成界面。在各种人类癌症中都观察到异常表达的糖酐异常。本研究评估胰导管腺癌（PDAC）中糖酐异常的表达，并分析其与临床指标的关系。通过实时定量PCR检测60例PDAC患者、48例CP患者和18例健康供体的组织样本中糖酐异常的mRNA水平。此外，我们对53例胰腺癌患者的标本进行免疫组织化学分析，使用特异性α -和β -糖酐异常抗体。使用Kaplan-Meier方法对染色进行半定量评估，并将其与患者生存率相关联。在mRNA水平上，与正常胰腺相比，PDAC中糖营养不良蛋白下调。在正常胰腺组织中，α -和β -异糖甘聚糖主要表达于腺泡和导管细胞的基底外侧细胞膜上，而胰岛细胞呈细胞质染色。相比之下，在PDAC组织中，这种膜染色模式消失，取而代之的是细胞质染色，这表明两种糖酐的膜易位受损。半定量分析显示α -糖酐异常染色与术后生存率呈显著负相关（P = 0.039）。糖醛酸异常蛋白的表达减少和定位改变在PDAC中很常见，可能导致这种疾病的侵袭性行为。(C) 2011爱思唯尔公司版权所有。
Background. Deregulation of cell-matrix interactions is considered an important factor in malignant transformation. Dystroglycan forms the interface between the basement membrane and the cell membrane in epithelia by its two subunits, alpha- and beta-dystroglycan. Aberrant expression of dystroglycan has been observed in various human cancers. Here we assessed the expression of dystroglycan in pancreatic ductal adenocarcinoma (PDAC) and analyzed its association with clinical parameters.Methods. mRNA levels of dystroglycan were determined by real-time quantitative PCR in tissue samples from 60 patients with PDAC, from 48 patients with CP, and from 18 healthy donors. Furthermore, pancreatic cancer specimens of 53 patients were analyzed by immunohistochemistry using specific alpha- and beta-dystroglycan antibodies. The staining was semiquantitatively evaluated and correlated to patient survival using the Kaplan-Meier method.Results. On the mRNA level, dystroglycan was down-regulated in PDAC compared with the normal pancreas. In normal pancreatic tissues, alpha- and beta-dystroglycans were mainly expressed on the basolateral cell membrane of acinar and ductal cells, while islet cells showed a cytoplasmatic staining. In contrast, in PDAC tissues, this membrane staining pattern was lost and replaced by a cytoplasmatic staining, suggesting impairments in the membrane translocation of both dystroglycans. Semiquantitative analysis revealed a significant inverse correlation of alpha- (but not beta-) dystroglycan staining and postoperative survival (P = 0.039).Conclusion. Reduced expression and altered localization of dystroglycan is common in PDAC, potentially contributing to the aggressive behavior of this disease. (C) 2011 Elsevier Inc. All rights reserved.