Usefulness of MALDI-TOF/MS identification of low-MW fragments in sera for the differential diagnosis of pancreatic cancer

Pancreas. 2013 May;42(4):622-32. doi: 10.1097/MPA.0b013e318273096c.

Abstract

Objectives: To identify new biomarkers of pancreatic cancer (PaCa), we performed MALDI-TOF/MS analysis of sera from 22 controls, 51 PaCa, 37 chronic pancreatitis, 24 type II diabetes mellitus (DM), 29 gastric cancer (GC), and 24 chronic gastritis (CG).

Methods: Sera were purified by Sep-Pak C18 before MALDI-TOF/MS Anchorchip analysis.

Results: Features present in at least 5% of all spectra were selected (n = 160, m/z range, 1200-5000). At univariate analysis, 2 features (m/z 2049 and 2305) correlated with PaCa, 3 (m/z 1449, 1605, and 2006) with DM. No feature characterized gastric cancer or chronic gastritis. Ten-fold cross-validation binary recursive partitioning trees were obtained for patients' classification. The tree (CA 19-9, age, m/z 2006, 2599, 2753, and 4997), built considering only patients with diabetes, allowed a distinction between DM [area under the receiver operating characteristic curve (AUC), 0.997], chronic pancreatitis (AUC, 0.968), and PaCa (AUC, 0.980), with an overall correct classification rate of 89%. The tree including CA 19-9, 1550, and 2937 m/z features, achieved an AUC of 0.970 in distinguishing localized from advanced PaCa. MALDI-TOF-TOF analysis revealed the 1550 feature as a fragment of Apo-A1, which was determined as whole protein and demonstrated to be closely correlated with PaCa.

Conclusions: The findings made demonstrate a role for serum peptides identified using MALDI-TOF/MS for addressing PaCa diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein A-I / blood
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / chemistry
  • CA-19-9 Antigen / blood
  • Case-Control Studies
  • Clusterin / blood
  • Complement C3 / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diagnosis, Differential
  • Female
  • Gastritis / blood
  • Gastritis / diagnosis
  • Humans
  • Male
  • Middle Aged
  • Molecular Weight
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatitis, Chronic / blood
  • Pancreatitis, Chronic / diagnosis
  • Peptide Fragments / blood*
  • Peptide Fragments / chemistry
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / diagnosis

Substances

  • Apolipoprotein A-I
  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • CLU protein, human
  • Clusterin
  • Complement C3
  • Peptide Fragments