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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 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 - 3 Aug 2015

Keywords

  • Colorectal cancer
  • Membrane proteins
  • Label free shotgun proteomics
  • Epidermal growth factor receptor
  • Fibronectin
  • Malectin

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