Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples
Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples
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DOI：
10.1016/j.pan.2011.12.003
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发表时间：
2012-01-01
期刊：
影响因子：
3.6
通讯作者：
Buscail, L.
中科院分区：
文献类型：
--
作者：
Bournet, B.;Pointreau, A.;Buscail, L.
目的：本研究的目的是探讨对局部晚期和/或转移性胰腺导管腺癌和慢性胰腺炎的内镜超声引导细针抽吸活检样本进行低密度阵列分析的临床可行性和实用性。 患者和方法：在这项前瞻性多中心研究中，我们使用专用方法对取自 44 例局部晚期和/或转移性胰腺癌和 17 例假瘤性慢性胰腺炎的活检样本中的候选基因表达进行了量化。结果：我们首先证明18S基因表达在正常胰腺和胰腺癌组织中是稳定且具有可比性的。接下来，我们发现与假瘤性慢性胰腺炎相比，胰腺癌样本中有八个基因（S100P、PLAT、PLAU、MSLN、MMP-11、MMP-7、KRT7、KRT17）显着过度表达（p 值范围为 0.0007 至 0.0215）：线性判别分析确定 S100P、PLAT、MSLN、MMP-7、KR77 高度表达。解释变量。受试者工作曲线下面积确定了本研究中确定的潜在诊断标志物的临床有效性（值范围为 0.69 至 0.76）。此外，S100P 和 KRT7 的组合提供了更好的诊断性能（接受者操作曲线下面积 0.81，敏感性 81%，特异性 77%）。结论：我们证明，EUS 引导下的 FNA 材料的分子研究对于诊断为不可切除肿瘤的 PDAC 患者的标记物的识别和定量是可行的。使用低密度阵列，我们分离了晚期胰腺癌的分子特征，其中主要包括与癌症侵袭相关的基因。这项工作源于使用新型生物标志物对胰腺实性肿块患者进行分子诊断。版权所有 (C) 2012，IAP 和 EPC。由 Reed Elsevier India Pvt. 旗下子公司 Elsevier India 出版。有限公司保留所有权利。
Aims: The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis.Patients and methods: In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates.Results: We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KR77 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%).Conclusion: We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.