Quantitative Proteomic and Genomic Profiling Reveals Metastasis-Related Protein Expression Patterns in Gastric Cancer Cells

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• 作者：Yet-Ran Chen ; Hsueh-Fen Juan ; Hsuan-Cheng Huang ; Hsin-Hung Huang ; Ya-Jung Lee ; Mei-Yueh Liao ; Chien-Wei Tseng ; Li-Ling Lin ; Jeou-Yuan Chen ; Mei-Jung Wang ; Jenn-Han Chen ; ; O ; Yu-Ju Chen
• 刊名：Journal of Proteome Research
• 出版年：2006
• 出版时间：October 2006
• 年：2006
• 卷：5
• 期：10
• 页码：2727 - 2742
• 全文大小：643K
• 年卷期：v.5,no.10(October 2006)
• ISSN：1535-3907

文摘

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