Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer

ABSTRACT: Gastric cancer (GC) is among the most aggressive malignancy affecting the world population. With almost a million cases remains in fifth position in incidence, while reaching the third position in mortality. The progression of GC is slow with several prolonged and sequential precancerous stages, including chronic gastritis, intestinal metaplasia, dysplasia and finally gastric cancer. Here we used the iTRAQ chemistry in combination with high-resolution mass spectrometry analysis to describe, from the proteomics point of view, the progression of the GC disease. Tissue samples from three stages: chronic gastritis, intestinal metaplasia and gastric adenocarcinoma, were selected for the quantitative proteomics analysis. From four independent replicates we identified and reported quantitative data for 3,914 different proteins with at least two unique peptides confidently quantified in all replicates. We uncovered pathways and processes dysregulated between the different stages. The initial transformation is characterized by the down-regulation of ribosomes and the protein processing in the endoplasmic reticulum, while overexpressing cell survival pathway and proteins such as GSTP1 and EPCAM. The transformation to GC involved the activation of DNA replication and Spliceosome pathways, overexpression of proteins supporting high rates of proliferation such as NPM1. In GC SIRT3 and SIRT5 were down-regulated, which correlated with the impairment of the mitochondrial pathways and overexpression of enzymes supporting the glycolytic phenotype such as HK3 and PCK2. Several proteins found dysregulated between stages of the progression of GC has potential to be used as specific biomarkers and/or targets for therapeutic treatment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stomach

DISEASE(S): Stomach Cancer

SUBMITTER: Jeovanis Gil  

LAB HEAD: Guadalupe Ayala Aguilar

PROVIDER: PXD008081 | Pride | 2019-09-27

REPOSITORIES: Pride