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Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis

 Manveen K. Sethi  ;  Morten Thaysen-Andersen  ;  Hoguen Kim  ;  Cheol Keun Park  ;  Mark S. Baker  ;  Nicolle H. Packer  ;  Young Ki Paik  ;  William S. Hancock  ;  Susan Fanayan 
 Journal of Proteomics, Vol.126 : 54-67, 2015 
Journal Title
 Journal of Proteomics 
Issue Date
Colorectal Neoplasms/metabolism* ; Colorectal Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic* ; Humans ; Male ; Neoplasm Proteins/biosynthesis* ; Proteome/biosynthesis* ; Proteomics* ; Signal Transduction*
Colorectal cancer ; Epidermal growth factor receptor ; Fibronectin ; Label free shotgun proteomics ; Malectin ; Membrane proteins
Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ho Keun(김호근)
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