Gastric cancer is a leading cause of death from
cancer globally.
Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify
proteins in
tumor tissues from patients with diffuse or intestinal
gastric cancer with adjacent normal tissue control. A total of 7448 or 4846
proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2),
olfactomedin 4 (OLFM4),
thyroid hormone receptor interacting protein 6 (TRIP6) and
melanoma-associated
antigen 9 (MAGE-A9)
proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in
tumor progression and
metastasis, they have not been linked to intestinal or diffuse subtypes of
gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of
gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these
gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.