Invasive markers identified by gene expression profiling in pancreatic cancer

Pancreatology. Mar-Apr 2012;12(2):130-40. doi: 10.1016/j.pan.2011.12.011. Epub 2011 Dec 31.

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).

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Adolescent
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • 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 / genetics*
  • 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

Substances

  • Biomarkers, Tumor
  • PLAUR protein, human
  • Receptors, Interleukin-1
  • Receptors, Urokinase Plasminogen Activator
  • Matrix Metalloproteinase 1
  • Tetradecanoylphorbol Acetate