Multidimensional Identification of Tissue Biomarkers of Gastric Cancer

Gastric cancer remains highly fatal due to a dearth of
diagnostic
biomarkers for early stage disease and molecular targets for therapy.
Plasma membrane proteins, including cluster of differentiation (CD)
proteins and receptor tyrosine kinases (RTKs), are a rich reservoir
of biomarkers. Recognizing that interrogating plasma membrane proteins
individually overlooks extensive interactions among them, we have
systematically investigated the membrane proteomes and transcriptomes
of six gastric cancer cell lines. Our data revealed aberrantly high
expression of proteins whose functions accurately reflect the clinical
phenotype of gastric cancer, and prioritized critical RTKs and CD
proteins in gastric cancer. Expression of selected surface proteins
was confirmed by flow cytometry and immunostaining of clinical gastric
cancer tissues. Close to 90% of the gastric cancer tissues in a cohort
showed up-regulation of at least one of four proteins, that is, MET,
EPHA2, FGFR2, and CD104/ITGB4. All intestinal type gastric cancer
tumors in this cohort overexpressed at least one of a panel of three
proteins, MET, FGFR2, and EPHA2. This study reports the first quantitative
global landscape of the surface proteome of gastric cancer cells and
provides a shortlist of gastric cancer biomarkers.