Protein expression profiling reveals distinctive changes in serum proteins associated with chronic pancreatitis

Pancreas. 2007 Nov;35(4):334-42. doi: 10.1097/mpa.0b013e3180cac723.

Abstract

Objective: Testing of serum for protein patterns to monitor progression of suspected to definite chronic pancreatitis (CP).

Methods: Serum samples of CP patients and healthy volunteers were fractionated on anion exchange columns and analyzed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry to elucidate CP-related protein alterations and to identify biomarkers for this disease. Potential biomarkers were purified and identified by mass spectrometry.

Results: In total, 258 protein peaks were found that discriminated between the 2 groups. Analysis revealed 28 most prominent peaks on immobilized metal affinity capture coupled with Cu and CM10 protein chips, covering the m/z range between 3.3 and 33.3 kd. Performing multivariate pattern analysis, the best pattern model was obtained using fraction 6 on immobilized metal affinity capture coupled with Cu arrays with a sensitivity of 96% and a specificity of 84%. Using a combination of matrix-assisted laser desorption-ionization-time-of-flight mass spectrometry and immunodepletion, we identified 14-m/z peaks. The proteins were found to be significantly decreased in CP serum and were identified as retinol-binding protein, serum amyloid-alpha, apolipoprotein A-II (Apo A-II), Apo C-I, Apo C-II, Apo C-III, and transthyretin and truncated forms thereof.

Conclusions: Distinct protein profile differences exist between normal and CP serum and reflect the metabolic and inflammatory condition in CP patients. The identified protein panel may eventually serve as a diagnostic marker set for CP.

MeSH terms

  • Adult
  • Amyloid / blood
  • Anion Exchange Resins
  • Apolipoprotein A-II / blood
  • Apolipoprotein C-I / blood
  • Apolipoprotein C-II / blood
  • Apolipoprotein C-III / blood
  • Biomarkers / blood
  • Blood Proteins / analysis*
  • Blood Proteins / isolation & purification
  • Case-Control Studies
  • Cluster Analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Ion Exchange
  • Male
  • Middle Aged
  • Pancreatitis, Chronic / blood*
  • Pancreatitis, Chronic / diagnosis
  • Prealbumin / analysis
  • Predictive Value of Tests
  • Protein Array Analysis / methods*
  • ROC Curve
  • Reproducibility of Results
  • Retinol-Binding Proteins, Plasma / analysis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • APOC1 protein, human
  • Amyloid
  • Anion Exchange Resins
  • Apolipoprotein A-II
  • Apolipoprotein C-I
  • Apolipoprotein C-II
  • Apolipoprotein C-III
  • Biomarkers
  • Blood Proteins
  • Prealbumin
  • Retinol-Binding Proteins, Plasma