title: In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic insight and identification of potential biomarkers.
abstract: 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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: gkaragiannis@mtsinai.on.ca.
authors.forename: George S
authors.initials: GS
authors.lastname: Karagiannis
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: mpavlou@mtsinai.on.ca.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Pavlou
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: punit.saraon@utoronto.ca.
authors.forename: Punit
authors.initials: P
authors.lastname: Saraon
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: Natasha.musrap@mtsinai.on.ca.
authors.forename: Natasha
authors.initials: N
authors.lastname: Musrap
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: anniexie31@gmail.com.
authors.forename: Annie
authors.initials: A
authors.lastname: Xie
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: ibatruch.acdclabs@gmail.com.
authors.forename: Ihor
authors.initials: I
authors.lastname: Batruch
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: yprassas@gmail.com.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Prassas
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Electronic address: apostol@cs.toronto.edu.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Dimitromanolakis
authors.affiliation: Pathology Department, Metropolitan Hospital, Athens, Greece. Electronic address: constantinapetraki@gmail.com.
authors.forename: Constantina
authors.initials: C
authors.lastname: Petraki
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada. Electronic address: ediamandis@mtsinai.on.ca.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C454127:OLFM4 protein, human; D020543:Proteome; D016179:Granulocyte Colony-Stimulating Factor
keywords: Colorectal cancer; Enrichment map analysis; Exoproteome; Kallikrein-related peptidase; Olfactomedin-4; Proteomics