Gastric cancer is a leading cause of death worldwide, and patients have an overall 5-year survival rate of less than 10%. Using quantitative proteomic techniques together with microarray chips, we have established comprehensive
proteome and transcriptome profiles of the metastatic
gastric cancer TMC-1 cells and the noninvasive
gastric cancer SC-M1 cell. Our qualitative
protein profiling strategy offers the first comprehensive analysis of the
gastric cancer cell
proteome, identifying 926 and 909
proteins from SC-M1 and TMC-1 cells, respectively. Cleavable
isotope-coded affinity tagging analysis allows quantitation of a total of 559
proteins (with a
protein false-positive rate of <0.005), and 240
proteins were differentially expressed (>1.3-fold) between the SC-M1 and TMC-1 cells. We identified numerous
proteins not previously associated with
gastric cancer. Notably, a large subset of differentially expressed
proteins was associated with
tumor metastasis, including
proteins functioning in cell-cell and cell-extracellular matrix (cell-ECM) adhesion, cell motility, proliferation, and
tumor immunity. Gene expression profiling by
DNA microarray revealed differential expression (of >2-fold) of about 1000 genes. The weak correlation observed between
protein and
mRNA profiles highlights the important complementarities of
DNA microarray and proteomics approaches. These comparative data enabled us to map the disease-perturbed cell-cell and cell-ECM adhesion and
Rho GTPase-mediated cytoskeletal pathways. Further validation of a subset of genes suggests the potential use of
vimentin and
galectin 1 as markers for
metastasis. We demonstrate that combining proteomic and genomic approaches not only provides a rapid, robust, and sensitive platform to elucidate the molecular mechanisms underlying
gastric cancer metastasis but also may identify candidate diagnostic markers and therapeutic targets.