Invasive markers identified by gene expression profiling in pancreatic cancer

作     者：Rogers, A. Smith, M. J. Doolan, P. Clarke, C. Clynes, M. Murphy, J. F. McDermott, A. Swan, N. Crotty, P. Ridgway, P. F. Conlon, K. C. 

作者机构：Adelaide & Meath Hosp Inc Natl Childrens Hosp Trinity Coll Dublin Dept Surg Dublin 24 Ireland Adelaide & Meath Hosp Inc Natl Childrens Hosp Trinity Coll Dublin Dept Histopathol Dublin 24 Ireland Dublin City Univ Natl Inst Cellular Biotechnol Dublin 9 Ireland 

出 版 物：《PANCREATOLOGY》 (胰腺病学)

年 卷 期：2012年第12卷第2期

页      面：130-140页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Meath Foundation 

主　　题：Adenocarcinoma/drug therapy Adenocarcinoma/genetics Adenocarcinoma/secondary Adolescent Aged Aged, 80 and over Cell Line, Tumor Cell Survival/drug effects Female Gene Expression Gene Expression Profiling Humans Male Matrix Metalloproteinase 1/genetics Matrix Metalloproteinase 1/metabolism Middle Aged Neoplasm Invasiveness/genetics Neoplasm Invasiveness/pathology Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms/drug therapy Pancreatic Neoplasms/drug therapy Pancreatic Neoplasms/genetics Pancreatic Neoplasms/genetics Pancreatic Neoplasms/pathology Pancreatic Neoplasms/pathology Real-Time Polymerase Chain Reaction Receptors, Interleukin-1/genetics Receptors, Interleukin-1/metabolism Receptors, Urokinase Plasminogen Activator/genetics Receptors, Urokinase Plasminogen Activator/metabolism Tetradecanoylphorbol Acetate/pharmacology Tumor Markers, Biological 

摘      要：Background: Molecular profiling has proven utility as a diagnostic and predictive tool in clinical oncology. However, a clinically relevant gene expression profile in pancreatic cancer remains elusive. Methods: Primary and metastatic pancreatic cancer cell lines (BxPC-3 and AsPC-1), were stimulated with phorbol-12-myristate 13-acetate (PMA), a known inducer of cell invasion. Affymetrix gene expression microarray analysis was performed, comparing gene expression to unstimulated controls. Differential expression was identified using ArrayAssist, and confirmed using quantitative real-time PCR. Bioinformatic analysis was performed using Pathway Studio and GOstat. The derived gene expression was further validated in fresh frozen pancreatic tumour samples. The ability of the derived 3 gene expression markersto differentiate between pancreatic adenocarcinoma (PDAC) and other neoplasms, and its association with clinicopathological variables was examined. Results: PMA-induced significant changes in cell line gene expression, from which distinctive 3 potential invasive markers were derived. Expression of these genes, uPA, MMP-1 and IL1-R1 was confirmed in human pancreatic tumours, and was found to differentiate PDAC from other pancreatic neoplasms. The expression of IL1-R1 in PDAC is a novel finding. We found that the expression of MMP-1 was associated with high-grade PDAC (p = 0.035, Wilcoxon rank sum). Conclusion: We have identified three potential invasive markers, uPA, MMP-1 and IL1-R1, whose gene expression may differentiate PDAC from other pancreatic neoplasms, and potentially reflect a more invasive phenotype. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.