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    A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome
    Graphical Abstract
    d Secreted proteins with elevated expression in tumors comprise potential biomarkers
    d Secretome expression changes common to many cancer types tend to be decreases
    d Common expression increases include functions such as extracellular matrix turnover
    d Tumors appear to reduce their tissue-specific secretome to relieve secretory stress 
    Jonathan L. Robinson, Amir Feizi, Mathias Uhle´n, Jens Nielsen
    [email protected]
    In Brief
    Robinson et al. compare secreted protein expression changes across different cancer types and healthy tissues to identify candidate biomarkers likely to be detectable in biological fluids. Functional analyses reveal a pattern whereby cancers decrease the expression of secreted proteins responsible for tissue of origin function in favor of those supporting proliferation and invasion.
    Cell Reports Article
    A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome
    Jonathan L. Robinson,1,2 Amir Feizi,1,5 Mathias Uhle´n,3,4 and Jens Nielsen1,2,3,4,6,* 1Department of Biology and Biological Engineering, Chalmers University of Technology, Kemiva¨gen 10, Gothenburg, Sweden 2Wallenberg Centre for Protein Research, Chalmers University of Technology, Kemiva¨gen 10, Gothenburg, Sweden 3Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden 4Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark 5Present address: Novo Nordisk Research Centre Oxford, Old Campus Road, Oxford, UK 6Lead Contact *Correspondence: [email protected]
    The collection of proteins secreted from a cell—the secretome—is of particular interest in cancer patho-physiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the asso-ciated functions. We therefore conducted a pan-can-cer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome pro-teins for each cancer. Furthermore, we offer a poten-tial mechanism by which cancer cells relieve secre-tory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and prolif-eration. These results provide a more systematic un-derstanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.