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.
Bibliographical noteFunding Information:
This research was facilitated through access to Australian Proteomics Analysis Facility (APAF) and funds from 2013 NTRCU research scholar award and Macquarie research scholarship . We thank Dr. Hyoung-Joo Lee and Mr. Jong-Sun Lim for the assistance with mass spectrometry. We thank Dr. Dana Pascovici for assistance with statistical analysis. M.T.A. was supported by an Early Career Development Fellowship from the Cancer Institute, NSW, Australia.
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