Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer

Julia M. Humphries, Megan A S Penno, Florian Weiland, Manuela Klingler-Hoffmann, Agnieszka Zuber, Alex Boussioutas, Matthias Ernst, Peter Hoffmann

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31 Citations (Scopus)

Abstract

The timely detection of gastric cancer will contribute significantly towards effective treatment and is aided by the availability and reliability of appropriate biomarkers. A combination of several biomarkers can improve the sensitivity and specificity of cancer detection and this work reports results from a panel of 4 proteins. By combining a validated preclinical mouse model with a proteomic approach we have recently discovered novel biomarkers for the detection of gastric cancer. Here, we investigate the specificity of four of those biomarkers (afamin, clusterin, VDBP and haptoglobin) for the detection of gastric cancer using two independent methods of validation: ELISA, and a non antibody based method: Multiple Reaction Monitoring with High Resolution Mass Spectrometry (MRM-HR). All four biomarkers reliably differentiated GC from benign patient serum, and also in a small cohort of 11 early stage cases. We also present a novel isoform specific biomarker alpha-1-antitrypsin (A1AT) that was identified using a mouse model for gastric cancer. This isoform is distinct in charge and mobility in a pH gradient and was validated using human samples by isoelectric focussing and Western-blot (IEF-WB). This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

Original languageEnglish
Pages (from-to)1051-1058
Number of pages8
JournalBBA Proteins and Proteomics
Volume1844
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Biomarkers
  • Intestinal-type gastric adenocarcinoma
  • Isoforms
  • Post-translational modifications
  • Serum proteomics

Cite this

Humphries, J. M., Penno, M. A. S., Weiland, F., Klingler-Hoffmann, M., Zuber, A., Boussioutas, A., Ernst, M., & Hoffmann, P. (2014). Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer. BBA Proteins and Proteomics, 1844(5), 1051-1058. https://doi.org/10.1016/j.bbapap.2014.01.018