Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer
Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer
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DOI：
10.1002/ijc.21317
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发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Tanaka, M
中科院分区：
文献类型：
--
作者：
Ohuchida, K;Mizumoto, K;Tanaka, M
胰液是一种很有前途的胰腺癌诊断样本，而粘蛋白(MUC)家族成员是诊断候选对象。为了评价MUC家族成员作为诊断标记物的价值，我们用实时荧光定量聚合酶链式反应检测了不同胰腺疾病患者的胰腺组织和胰液以及胰腺癌细胞系中MUC基因的表达。此外，为了支持MUC1和MUC5AC定量诊断的可能性，进行了免疫组织化学和显微解剖定量分析。MUC1和MUC5AC在细胞系中的表达无明显相关性。当以β-肌动蛋白为参照基因时，肿瘤组织中MUC1mRNA和MUC5ACmRNA的表达水平显著高于非肿瘤组织，而MUC4和MUC6mRNA的表达水平则无显著差异。受试者工作特征曲线分析显示，定量检测胰液中MUC1mRNA和MUC5ACmRNA值优于MUC4和MUC6mRNA值。免疫组织化学结果显示，MUC1和MUC5AC在浸润性导管癌(IDC)中高表达，在高级别胰腺上皮内瘤变(PanIN)中低表达，在正常导管组织中未见表达。显微解剖分离的细胞分析显示，在高级别Panin向IDC的发展过程中，MUC1和MUC5AC的表达逐渐上调。结果提示，MUC1和MUC5AC在胰腺癌的发生发展过程中呈阶段性上调，检测胰液中MUC1和MUC5AC的mRNA水平对胰腺癌的术前诊断具有较高的临床应用价值。(C)2005年Wiley-Liss。Inc.
Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer. (c) 2005 Wiley-Liss. Inc.