Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study

J Proteome Res. 2012 Mar 2;11(3):1937-48. doi: 10.1021/pr201117w. Epub 2012 Feb 8.


Biomarkers are most frequently proteins that are measured in the blood. Their development largely relies on antibody creation to test the protein candidate performance in blood samples of diseased versus nondiseased patients. The creation of such antibody assays has been a bottleneck in biomarker progress due to the cost, extensive time, and effort required to complete the task. Targeted proteomics is an emerging technology that is playing an increasingly important role to facilitate disease biomarker development. In this study, we applied a SRM-based targeted proteomics platform to directly detect candidate biomarker proteins in plasma to evaluate their clinical utility for pancreatic cancer detection. The characterization of these protein candidates used a clinically well-characterized cohort that included plasma samples from patients with pancreatic cancer, chronic pancreatitis, and healthy age-matched controls. Three of the five candidate proteins, including gelsolin, lumican, and tissue inhibitor of metalloproteinase 1, demonstrated an AUC value greater than 0.75 in distinguishing pancreatic cancer from the controls. In addition, we provide an analysis of the reproducibility, accuracy, and robustness of the SRM-based proteomics platform. This information addresses important technical issues that could aid in the adoption of the targeted proteomics platform for practical clinical utility.

Publication types

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

MeSH terms

  • 14-3-3 Proteins / blood
  • 14-3-3 Proteins / chemistry
  • Amino Acid Sequence
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / chemistry
  • Carcinoma, Pancreatic Ductal / blood*
  • Case-Control Studies
  • Chondroitin Sulfate Proteoglycans / blood
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Exonucleases / blood
  • Exonucleases / chemistry
  • Exoribonucleases
  • Gelsolin / blood
  • Gelsolin / chemistry
  • Humans
  • Keratan Sulfate / blood
  • Keratan Sulfate / chemistry
  • Lumican
  • Molecular Sequence Data
  • Pancreatic Neoplasms / blood*
  • Peptide Fragments / chemistry
  • Peptide Mapping
  • Pilot Projects
  • Proteomics
  • ROC Curve
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinase-1 / chemistry


  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • Chondroitin Sulfate Proteoglycans
  • Gelsolin
  • LUM protein, human
  • Lumican
  • Peptide Fragments
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Keratan Sulfate
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human