Novel Candidate Protein Biomarkers for Human Gastric Cancer — ASN Events

Novel Candidate Protein Biomarkers for Human Gastric Cancer (#445)

Julia M Humphries 1 , Megan AS Penno 2 , Alex Boussioutas 3 , Matthias Ernst 4 , Peter Hoffmann 1
  1. Adelaide Proteomics Centre, The University of Adelaide, Adelaide, SA, Australia
  2. Department of Paediatrics, Women's and Children's Hospital, The University of Adelaide, Adelaide, SA, Australia
  3. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
  4. Ludwig Institute for Cancer Research, Parkville, Victoria, Australia

Gastric cancer (GC) is the second leading cause of cancer death worldwide with a 5-year survival rate of < 30%.The late diagnosis of gastric cancer (GC) significantly reduces average patient survival times. Existing methods for early-stage GC detection are invasive and/or cost-prohibitive for many populations. A blood test based on reliable protein biomarkers for early detection is needed.
Previously the differential expression of 112 2D-DIGE spots specifically correlated with the tumour-bearing phenotype, corresponding to 31 murine proteins and their 28 human orthologues were identified. A subset of these proteins was selected for validation in GC patient sera versus healthy controls (GC n=13, Ctrl n=13). ELISAs performed on the 8 proteins in human sera revealed significant increases in serum apolipoprotein E and haptoglobin, and decreases in afamin and clusterin. Receiver operating characteristic (ROC) analysis revealed that afamin, apoE, clusterin and haptoglobin were more sensitive and specific discriminators of GC than a currently implemented clinical marker CA 72-41, as determined by ROC.
Candidate GC biomarkers identified in murine (gp130F/F) model were successfully translated to humans for biomarker discovery. Differential isoforms of these proteins will be fractionated using the Protein Forest dPC based on their pI, for identification of post-translational modifications which have been show to be clinically relevant. Early GC will be compared with Late GC and Controls to explore the clinical utility of these candidate biomarkers in preoperative GC patients.