| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1226583 | Journal of Proteomics | 2012 | 19 Pages |
The gp130F/F genetically engineered mouse (GEM) model reproducibly and predictably develops a gastric adenoma phenotype resembling the primary lesions of human intestinal-type gastric cancer (GC). Accordingly, changes to the serum proteome of gp130F/F mice may uncover early-stage GC biomarkers. Here, we have employed several double and compound mutant GEM strains that display distinct phenotypes with respect to gastric tumour load and inflammatory response, thereby mimicking different states of inflammation-associated early-stage GC in humans. This allowed us to distinguish between proteomic changes associated with tumourigenesis rather than confounding systemic inflammation. The comparative proteomic workflow involved depletion of high abundance proteins, 2D-DIGE analysis and protein identification by LC-MS/MS. 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. Eight proteins were selected for validation in GC patient sera versus healthy controls. Significant increases in serum apolipoprotein E and haptoglobin, and decreases in afamin and clusterin, were confirmed by ELISA. Receiver operating characteristic analysis revealed that these proteins may be more sensitive and specific discriminators of GC than the existing clinical marker CA72-4.
Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (285 K)Download as PowerPoint slideHighlights► Mouse model of GC provides basis for an unbiased serum protein biomarker screen. ► Genetic partitioning stratifies inflammation- and tumour-associated proteins. ► 2D-DIGE/LC-MS/MS yields 8 tumour-associated proteins reflecting a host response. ► Altered levels of afamin, clusterin, haptoglobin and apoE confirmed in GC patients.
