In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic insight and identification of potential biomarkers

• Published in: Journal of proteomics 2014-05, Vol.103, p.121-136
• Main Authors: Karagiannis, George S., Pavlou, Maria P., Saraon, Punit, Musrap, Natasha, Xie, Annie, Batruch, Ihor, Prassas, Ioannis, Dimitromanolakis, Apostolos, Petraki, Constantina, Diamandis, Eleftherios P.
• Format: Article
• Language: English
• Subjects: Colorectal cancer; Enrichment map analysis; Exoproteome; Kallikrein-related peptidase; Olfactomedin-4; Proteomics
• ISSN: 1874-3919
• DOI: 10.1016/j.jprot.2014.03.018

Systemic mining of cancer exoproteome/secretome has emerged as a pivotal strategy for delineation of molecular pathways with mechanistic importance in cancer development, as well as the discovery of diagnostic/prognostic biomarkers. Although major advances in diagnostic and therapeutic management of colorectal cancer have been underscored in the last decade, this cancer still remains the second leading cause of cancer-related deaths in the developed world. Despite previous studies on deciphering the colorectal cancer exoproteome, such studies lack adequate depth and robustness due to technological limitations. Here, using a well-established LC–MS/MS method on an LTQ-Orbitrap mass spectrometer, we extensively delineated the exoproteome of 12 colon cancer cell lines. In total, 2979 non-redundant proteins were identified with a minimum of two peptides, of which ~62% were extracellular or cell membrane-bound, based on prediction software. To further characterize this dataset and identify clinical opportunities, first, we investigated overrepresented molecular concepts of interest via enrichment map analysis and second, we demonstrated translational importance of certain proteins, such as olfactomedin-4 and kallikrein-related peptidases-6 and -10, by investigating their expression levels in patient tissues and/or fluids. Overall, the present study details a comprehensive colorectal cancer exoproteome dataset, and may be used as future platform for biomarker discovery, and hypothesis-generating studies. This article represents one of the most extensive and comprehensive proteomic datasets regarding the secreted/extracellular proteome of colorectal cancer cell lines. The reported datasets may form a platform for a plethora of future, discovery-based or hypothesis-generating studies, attempting to either delineate putative cancer biomarkers for CRC, or elucidate questions of mechanistic importance (e.g. investigation of deregulated pathways for CRC progression). [Display omitted] •Proteomic analysis of 12 colon cancer (CRC) cell line supernatants was performed.•The extracellular proteome of CRC was characterized.•Enrichment map analysis defined overrepresented molecular pathways.•Kallikrein-related peptidases-6 and -10 were validated in human tissues.•Olfactomedin-4 was proposed as potential serological biomarker for CRC.