Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling
Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling
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DOI：
10.1111/j.1349-7006.2009.01359.x
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Noda, Tetsuo
中科院分区：
文献类型：
--
作者：
Hirono, Seiko;Yamaue, Hiroki;Noda, Tetsuo
淋巴结转移（LNM）是胰管腺癌（PDAC）手术切除患者最重要的预后因素。在这项研究中，我们旨在通过全基因组表达谱鉴定PDAC中与LNM相关的分子标记。在这项研究中，我们使用激光显微解剖和全基因组转录谱来鉴定来自20名PDAC患者的PDAC细胞中有和没有LNM的差异表达基因。免疫组织化学染色在另外43例患者中证实了这些标记物的临床意义。结果，微阵列分析鉴定出46个基因在PDAC中有LNM和无LNM表达差异，具有一定的意义。在另外一组验证患者中，通过免疫组织化学染色验证了其中四种生物标志物与PDAC中LNM的关联。在63例PDAC患者中，多因素分析显示PDAC的显著预测因子为激活增强子结合蛋白2 （AP2 α）低表达（P = 0.012）和粘蛋白17 （MUC17）高表达（P = 0.0192）。此外，多因素分析显示，AP2 α -低表达和muc17 -高表达是总生存差的独立预后因素（P分别为0.0012、0.0001）。由此可见，AP2 α和MUC17是与PDAC LNM相关的独立标志物。这两个标志物也与切除PDAC患者的生存相关。我们证明AP2 α和MUC17可能作为PDAC患者LNM的潜在预后分子标志物。（癌症科学2009）。
Lymph node metastasis (LNM) is the most important prognostic factor in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). In this study, we aimed to identify molecular markers associated with LNM in PDAC using genome-wide expression profiling. In this study, laser microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between PDAC cells with and without LNM obtained from 20 patients with PDAC. Immunohistochemical staining was used to confirm the clinical significance of these markers in an additional validation set of 43 patients. In the results, microarray profiling identified 46 genes that were differently expressed between PDAC with and without LNM with certain significance. Four of these biomarkers were validated by immunohistochemical staining for association with LNM in PDAC in an additional validation set of patients. In 63 patients with PDAC, significant LNM predictors in PDAC elucidated from multivariate analysis were low expression of activating enhancer binding protein 2 (AP2 alpha) (P = 0.012) and high expression of mucin 17 (MUC17) (P = 0.0192). Furthermore, multivariate analysis revealed that AP2 alpha-low expression and MUC17-high expression are independent prognostic factors for poor overall survival (P = 0.0012, 0.0001, respectively). In conclusion, AP2 alpha and MUC17 were independent markers associated with LNM of PDAC. These two markers were also associated with survival in patients with resected PDAC. We demonstrate that AP2 alpha and MUC17 may serve as potential prognostic molecular markers for LNM in patients with PDAC. (Cancer Sci 2009).