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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Eight pairs of primary CRC tissue samples and their corresponding adjacent non-tumorigenic colon tissues, derived from individuals suffering from clinically diagnosed CRC, were obtained from the archives of the Department of Pathology, Yonsei University (Seoul, South Korea) and the Liver Cancer Specimen Bank of the National Research Resource Bank program of the Korea Science and Engineering Foundation of the Ministry of Science and Technology (Seoul, South Korea). The tissues were diagnosed and staged for CRC by a pathologist at the Severance Hospital (Yonsei University, Seoul, South Korea). These samples were obtained for research purpose with authorization from the Institutional Review Board of the College of Medicine at Yonsei University (Seoul, South Korea) with informed consent of the involved subjects. All CRC primary tumors were adenocarcinomas obtained from seven male and one female patients varying in age, sites (i.e., sigmoid, transverse, rectum) and TNM-stages (I–IV), Table 1 A .
© 2015 Elsevier B.V.
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