Differential gene expression analysis of peripheral blood mononuclear cells reveals novel test for early detection of pancreatic cancer

Cancer Biomark. 2011;11(1):1-14. doi: 10.3233/CBM-2012-0260.

Abstract

Background: We sought to validate global microarray results indicating the differential expression of 383 genes in Peripheral Blood Mononuclear Cells (PBMCs) from patients with pancreatic cancer (PC) and to further evaluate their PC diagnostic potential.

Methods and materials: In total, 177 patients were recruited (47 healthy controls (HC), 35 chronic pancreatitis (CP) patients, and 95 PC patients). PBMC expressions of six genes from our previous study (ANXA3, ARG1, CA5B, F5, SSBP2, and TBC1D8) along with four new genes (MIC1, NGAL, MUC1, and MUC16) were analyzed using multiplex Q-RT PCR.

Results: Differential expressions of 5 of the 6 genes previously identified by PBMC microarray were validated in this study. Multivariate models for PBMC gene expression were attempted to determine if any combination was diagnostically superior to CA19-9 alone. We found that addition of PBMC CA5B, F5, SSBP2, and MIC1 expression levels to CA19-9 significantly improved CA19-9's diagnostic abilities when comparing resectable PC to CP patients (p=0.023).

Conclusions: Results of our previous study were validated, indicating reproducibility of PC-associated PBMC expression profiling. We identified a score-based model that can differentiate resectable PC from CP better than CA19-9, potentiating that PBMC differential expression analysis may offer a novel tool for early PC diagnosis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Area Under Curve
  • CA-19-9 Antigen / genetics
  • CA-19-9 Antigen / metabolism
  • Carbonic Anhydrase V / genetics
  • Carbonic Anhydrase V / metabolism
  • Case-Control Studies
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Early Detection of Cancer*
  • Factor V / genetics
  • Factor V / metabolism
  • Female
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques
  • Multiplex Polymerase Chain Reaction
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic
  • Transcriptome

Substances

  • CA-19-9 Antigen
  • DNA-Binding Proteins
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • SSBP2 protein, human
  • Factor V
  • Carbonic Anhydrase V