title: Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.
abstract: 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.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Manveen K
authors.initials: MK
authors.lastname: Sethi
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Morten
authors.initials: M
authors.lastname: Thaysen-Andersen
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baker
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors.forename: Nicolle H
authors.initials: NH
authors.lastname: Packer
authors.affiliation: Yonsei Proteome Research Center, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
authors.affiliation: Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2109, Australia; Barnett Institute, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Hancock
authors.affiliation: Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2109, Australia. Electronic address: susan.fanayan@mq.edu.au.
authors.forename: Susan
authors.initials: S
authors.lastname: Fanayan
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome
keywords: Colorectal cancer; Epidermal growth factor receptor; Fibronectin; Label free shotgun proteomics; Malectin; Membrane proteins