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

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...

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Veröffentlicht in:Journal of proteome research 2006-10, Vol.5 (10), p.2727-2742
Hauptverfasser: Chen, Yet-Ran, Juan, Hsueh-Fen, Huang, Hsuan-Cheng, Huang, Hsin-Hung, Lee, Ya-Jung, Liao, Mei-Yueh, Tseng, Chien-Wei, Lin, Li-Ling, Chen, Jeou-Yuan, Wang, Mei-Jung, Chen, Jenn-Han, Chen, Yu-Ju
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container_end_page 2742
container_issue 10
container_start_page 2727
container_title Journal of proteome research
container_volume 5
creator Chen, Yet-Ran
Juan, Hsueh-Fen
Huang, Hsuan-Cheng
Huang, Hsin-Hung
Lee, Ya-Jung
Liao, Mei-Yueh
Tseng, Chien-Wei
Lin, Li-Ling
Chen, Jeou-Yuan
Wang, Mei-Jung
Chen, Jenn-Han
Chen, Yu-Ju
description 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 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. Keywords: cICAT • 2D-LC−MS/MS • Mass Spectrometry • Gastric Cancer • Metastasis
doi_str_mv 10.1021/pr060212g
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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 &lt;0.005), and 240 proteins were differentially expressed (&gt;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 &gt;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. 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Proteome Res</addtitle><description>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 &lt;0.005), and 240 proteins were differentially expressed (&gt;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 &gt;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. 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Proteome Res</addtitle><date>2006-10</date><risdate>2006</risdate><volume>5</volume><issue>10</issue><spage>2727</spage><epage>2742</epage><pages>2727-2742</pages><issn>1535-3893</issn><eissn>1535-3907</eissn><abstract>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 &lt;0.005), and 240 proteins were differentially expressed (&gt;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 &gt;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. Keywords: cICAT • 2D-LC−MS/MS • Mass Spectrometry • Gastric Cancer • Metastasis</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>17022644</pmid><doi>10.1021/pr060212g</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record>
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subjects Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Cell Adhesion - genetics
Cell Movement - genetics
Cell Proliferation
Gene Expression
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Genomics - methods
Humans
Neoplasm Metastasis
Neoplasm Proteins - analysis
Neoplasm Proteins - genetics
Oligonucleotide Array Sequence Analysis
Protein Biosynthesis - genetics
Proteomics - methods
RNA, Messenger - analysis
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Tumor Cells, Cultured
title Quantitative Proteomic and Genomic Profiling Reveals Metastasis-Related Protein Expression Patterns in Gastric Cancer Cells
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