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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)54-67
Number of pages14
JournalJournal of Proteomics
Volume126
DOIs
Publication statusPublished - 2015 Aug 3

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Proteomics
Colorectal Neoplasms
Tissue
Neoplasm Metastasis
Proteome
Tumors
Proteins
Neoplasms
Annexins
Deregulation
Ribosomal Proteins
Cluster analysis
Cell Adhesion Molecules
Actin Cytoskeleton
Cluster Analysis
Labels
Actins
Down-Regulation
Membranes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

Cite this

Sethi, Manveen K. ; Thaysen-Andersen, Morten ; Kim, Hoguen ; Park, Cheol Keun ; Baker, Mark S. ; Packer, Nicolle H. ; Paik, Young-Ki ; Hancock, William S. ; Fanayan, Susan. / Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis. In: Journal of Proteomics. 2015 ; Vol. 126. pp. 54-67.
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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. / Sethi, Manveen K.; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S.; Packer, Nicolle H.; Paik, Young-Ki; Hancock, William S.; Fanayan, Susan.

In: Journal of Proteomics, Vol. 126, 03.08.2015, p. 54-67.

Research output: Contribution to journalArticle

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