Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients Miguel-Pérez, Diego de Rodríguez Martínez, Alba Ortigosa Palomo, Alba Delgado Ureña, Mayte García Puche, José Luis Robles Remacho, Agustín Expósito Hernández, José Lorente Acosta, José Antonio Ortega Sánchez, Francisco Gabriel Serrano, María José Colorectal cancer Tumour biomarkers We would like to extend our gratitude to the all the patients and the healthy volunteers who participated in the study, as well as the University of Granada, Biomedicine PhD program. This work was supported by Roche Spain, the PhD grant from the University of Granada (DdMP) (2014) and the PhD grant from the Spanish Government (ARM) (FPU) 2014, REF FPU14/05461. Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC. 2020-11-13T12:17:19Z 2020-11-13T12:17:19Z 2020-03-04 journal article de Miguel Pérez, D., Rodriguez Martínez, A., Ortigosa Palomo, A. et al. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients. Sci Rep 10, 3974 (2020). [https://doi.org/10.1038/s41598-020-60212-1] http://hdl.handle.net/10481/64260 10.1038/s41598-020-60212-1 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Springer Nature