Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays

Neoplasia. Sep-Oct 2004;6(5):611-22. doi: 10.1593/neo.04295.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy-related death and is the eighth most common cancer with the lowest overall 5-year relative survival rate. To identify new molecular markers and candidates for new therapeutic regimens, we investigated the gene expression profile of microdissected cells from 11 normal pancreatic ducts, 14 samples of PDAC, and 4 well-characterized pancreatic cancer cell lines using the Affymetrix U133 GeneChip set. RNA was extracted from microdissected samples and cell lines, amplified, and labeled using a repetitive in vitro transcription protocol. Differentially expressed genes were identified using the significance analysis of microarrays program. We found 616 differentially expressed genes. Within these, 140 were also identified in PDAC by others, such as Galectin-1, Galectin-3, and MT-SP2. We validated the differential expression of several genes (e.g., CENPF, MCM2, MCM7, RAMP, IRAK1, and PTTG1) in PDAC by immunohistochemistry and reverse transcription polymerase chain reaction. We present a whole genome expression study of microdissected tissues from PDAC, from microdissected normal ductal pancreatic cells and pancreatic cancer cell lines using high-density microarrays. Within the panel of genes, we identified novel differentially expressed genes, which have not been associated with the pathogenesis of PDAC before.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Chromosomal Proteins, Non-Histone / analysis
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Microdissection
  • Microfilament Proteins
  • Middle Aged
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 7
  • Nuclear Proteins / analysis
  • Nuclear Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Microfilament Proteins
  • Nuclear Proteins
  • centromere protein F
  • MCM2 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Minichromosome Maintenance Complex Component 7