The secretome of highly metastatic cells as a source of biomarkers and metastatic effectors in colorectal cancer patients.

Introduction: Colorectal cancer (CRC) is the second leading cause of death in developed countries, mainly as a consequence metastatic spread. Secreted proteins are essential to communicate cells with tumor- microenvironment, favoring tumor progression and metastasis. The conditioned medium or cellular secretome, including exosomes, has demonstrated be rich source effectors biomarkers metastatization different tumors. Our goal was identify altered secreted fraction highly order determine biological pathways potential prognosis. Material methods: A quantitative label-free proteomic analysis carried out on secretome poorly CRC cell lines from genetic background. Proteomic results were validated using unbiased transcriptomic analyses. Hazard ratios long-rank tests for differentially-secreted determined four external datasets select clinical relevance further analysis. Gene ontology performed processes cells. Results: 221 found significantly associated Some corresponding genes able predict overall free survival stage II III patients. In addition, they showed higher expression stem cell-like CMS4 subtypes CRC, worse These also deficient mismatch repair, CpG-island methylator positive status BRAF mutation. It remarkable that significant number involved cholesterol metabolism, suggesting an enhancement LDL uptake metabolism Extracellular matrix constituents adhesion migration overrepresented fraction. Conclusion: Secretome enriched metastasis such us adhesion, lipid metabolism. several robust prognosis value detected howing biomarkers.