Protein expression profiling reveals distinctive changes in serum proteins associated with chronic pancreatitis.
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.
Hartmann
Daniel
D
Research Laboratory, European Center for Pancreas Research, Section for Pancreas Surgery and Molecular Research, Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Felix
Klaus
K
Ehmann
Michael
M
Schnölzer
Martina
M
Fiedler
Sabine
S
Bogumil
Ralf
R
Büchler
Markus
M
Friess
Helmut
H
D000328:Adult; D000682:Amyloid / Q000097:blood; D000837:Anion Exchange Resins; D016633:Apolipoprotein A-II / Q000097:blood; D053302:Apolipoprotein C-I / Q000097:blood; D053304:Apolipoprotein C-II / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis* / Q000302:isolation & purification; D016022:Case-Control Studies; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007474:Ion Exchange; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000097:blood* / Q000175:diagnosis; D011228:Prealbumin / Q000032:analysis; D011237:Predictive Value of Tests; D040081:Protein Array Analysis / Q000379:methods*; D012372:ROC Curve; D015203:Reproducibility of Results; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C505803:APOC1 protein, human; D000682:Amyloid; D000837:Anion Exchange Resins; D016633:Apolipoprotein A-II; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D015415:Biomarkers; D001798:Blood Proteins; D011228:Prealbumin; D054839:Retinol-Binding Proteins, Plasma