A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome

Abstract

Summary: The collection of proteins secreted from a cell—the secretome—is of particular interest in cancer pathophysiology 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 associated functions. We therefore conducted a pan-cancer 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 proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development. : 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. Keywords: secretome, protein secretion, cancer biomarkers, unfolded protein response, pan-cancer, systems biology