title: Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer.
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.
authors: Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: julia.humphries@health.sa.gov.au.
authors: Julia M
authors: JM
authors: Humphries
authors: Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: megan.penno@adelaide.edu.au.
authors: Megan A S
authors: MA
authors: Penno
authors: Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: florian.weiland@adelaide.edu.au.
authors: Florian
authors: F
authors: Weiland
authors: Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: manuela.klinglerhoffmann@adelaide.edu.au.
authors: Manuela
authors: M
authors: Klingler-Hoffmann
authors: Institute for Photonics & Advanced Sensing, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: agnieszka.zuber@adelaide.edu.au.
authors: Agnieszka
authors: A
authors: Zuber
authors: Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia; Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, VIC 8006, Australia.
authors: Alex
authors: A
authors: Boussioutas
authors: Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors: Matthias
authors: M
authors: Ernst
authors: Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: peter.hoffmann@adelaide.edu.au.
authors: Peter
authors: P
authors: Hoffmann
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D051152:Clusterin / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000175:diagnosis*; D006023:Glycoproteins / Q000097:blood; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis*; D014809:Vitamin D-Binding Protein / Q000097:blood; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: C088246:AFM protein, human; D014408:Biomarkers, Tumor; C495242:CLU protein, human; D002352:Carrier Proteins; D051152:Clusterin; D006023:Glycoproteins; C485359:HP protein, human; D006242:Haptoglobins; D020543:Proteome; D012709:Serum Albumin; D014809:Vitamin D-Binding Protein; D000515:alpha 1-Antitrypsin; D000075462:Serum Albumin, Human
keywords: Biomarkers; Intestinal-type gastric adenocarcinoma; Isoforms; Post-translational modifications; Serum proteomics