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.
BIOLOGICAL SIGNIFICANCE: 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).