title: Invasive markers identified by gene expression profiling in pancreatic cancer.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Trinity College Dublin, The Adelaide and Meath Hospital Incorporating the National Children's Hospital, Tallaght, Dublin 24, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Rogers
authors.forename: M J
authors.initials: MJ
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Doolan
authors.forename: C
authors.initials: C
authors.lastname: Clarke
authors.forename: M
authors.initials: M
authors.lastname: Clynes
authors.forename: J F
authors.initials: JF
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: McDermott
authors.forename: N
authors.initials: N
authors.lastname: Swan
authors.forename: P
authors.initials: P
authors.lastname: Crotty
authors.forename: P F
authors.initials: PF
authors.lastname: Ridgway
authors.forename: K C
authors.initials: KC
authors.lastname: Conlon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D017472:Receptors, Interleukin-1; D055293:Receptors, Urokinase Plasminogen Activator; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate