Applying Proteomic-Based Biomarker Tools for the Accurate Diagnosis of Pancreatic Cancer

  • Kyoko Kojima
  • Senait Asmellash
  • Christopher A. Klug
  • William E. Grizzle
  • James A. Mobley
  • John D. Christein
ssat plenary presentation

Abstract

Background

The proteome varies with physiologic and disease states. Few studies have been reported that differentiate the proteome of those with pancreatic cancer.

Aim

To apply proteomic-based technologies to body fluids. To differentiate pancreatic neoplasia from nonneoplastic pancreatic disease.

Methods

Samples from 50 patients (15 healthy (H), 24 cancer (Ca), 11 chronic pancreatitis (CP)) were prospectively collected and underwent analysis. A high-throughput method, using high-affinity solid lipophilic extraction resins, enriched low molecular weight proteins for extraction with a high-speed 200-Hz matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-MS; Bruker Ultraflex III). Samples underwent software processing with FlexAnalysis, Clinprot, MatLab, and Statistica (baseline, align, and normalize spectra). Nonparametric pairwise statistics, multidimensional scaling, hierarchical analysis, and leave-one-out cross validation completed the analysis. Sensitivity (sn) and specificity (sp) of group comparisons were determined. Two top-down-directed protein identification approaches were combined with MALDI-MS and tandem mass spectrometry to fully characterize the most significant protein biomarker.

Results

Using eight serum features, we differentiated Ca from H (sn 88%, sp 93%), Ca from CP (sn 88%, sp 30%), and Ca from both H and CP combined (sn 88%, sp 66%). In addition, nine features obtained from urine differentiated Ca from both H and CP combined with high efficiency (sn 90%, sp 90%). Interestingly, the plasma samples (considered by the Human Proteome Organization to be the preferred biological fluid) did not show significant differences. Multidimensional scaling indicated that markers from both serum and urine led to a highly effective clinical indicator of each specific disease state.

Conclusions

The proteomic analysis of noninvasively acquired biological fluids provided a high level of predictability for diagnosing pancreatic cancer. While the proteomic analysis of serum was capable of screening individuals for pancreatic disease (i.e., CP and Ca vs. H), specific urine biomarkers further distinguished malignancy (Ca) from chronic inflammation (CP).

Keywords

Pancreatic cancer Proteomics Mass spectrometry MALDI Serum 

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Copyright information

© The Society for Surgery of the Alimentary Tract 2008

Authors and Affiliations

  • Kyoko Kojima
    • 1
  • Senait Asmellash
    • 2
    • 5
  • Christopher A. Klug
    • 1
  • William E. Grizzle
    • 3
  • James A. Mobley
    • 4
  • John D. Christein
    • 5
  1. 1.Department of MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Biochemistry and Molecular GeneticsUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Department of PathologyUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Division of Urology, Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Section of Gastrointestinal Surgery, Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA

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