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

• Tight and separate clustering of tumor and normal tissues by hierarchical clustering of differentially expressed proteins
• Several deregulated cancer associated proteins identified, including FN1, EZR, TNC, DEFA1, MLEC, CDH17
• Several deregulated cancer associated pathways identified, including actin cytoskeleton and RhoGDI signaling
• Tumor stage-specific proteome signatures discovered
• EGFR-dependent down-regulation of cell adhesion molecules in EGFR+ CRC tissues

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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