Exploring the proteomic landscape of a gastric cancer biopsy with the shotgun imaging analyzer.

ABSTRACT

Accessing localized proteomic profiles has emerged as a fundamental strategy to understand the biology of diseases, as recently demonstrated, for example, in the context of determining cancer resection margins with improved precision. Here, we analyze a gastric cancer biopsy sectioned into 10 parts, each one subjected to MudPIT analysis. We introduce a software tool, named Shotgun Imaging Analyzer and inspired in MALDI imaging, to enable the overlaying of a protein's expression heat map on a tissue picture. The software is tightly integrated with the NeXtProt database, so it enables the browsing of identified proteins according to chromosomes, quickly listing human proteins never identified by mass spectrometry (i.e., the so-called missing proteins), and the automatic search for proteins that are more expressed over a specific region of interest on the biopsy, all of which constitute goals that are clearly well-aligned with those of the C-HPP. Our software has been able to highlight an intense expression of proteins previously known to be correlated with cancers (e.g., glutathione S-transferase Mu 3), and in particular, we draw attention to Gastrokine-2, a "missing protein" identified in this work of which we were able to clearly delineate the tumoral region from the "healthy" with our approach. Data are available via ProteomeXchange with identifier PXD000584.