1. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients
- Author
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Jose Luis Garcia Puche, Alba Rodríguez Martínez, José Exposito Hernandez, Diego Perez, Alba Ortigosa Palomo, Ma Jose Serrano, Agustín Robles Remacho, Francisco Gabriel Ortega Sánchez, Mayte Delgado Ureña, José Antonio Lorente Acosta, [de Miguel Pérez,D, Rodriguez Martínez,A, Ortigosa Palomo,A, Garcia Puche,JL, Robles Remacho,A, Lorente Acosta,JA, Serrano,MJ] GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Liquid biopsy and metastasis research group, PTS Granada, Granada, Spain. [de Miguel Pérez,D, Lorente Acosta,JA] Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain. [Delgado Ureña,M, Exposito Hernandez,J, Serrano,MJ] Integral Oncology Division, University Hospital Virgen de las Nieves, IBS Granada, Instituto de Investigación Biosanitaria de Granada, Granada, Spain. [Ortega Sánchez,FG] Balearic Islands Health Research Institute (IdISBa), Palma de Mallorca, Spain. [Ortega Sánchez,FG] Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands., and Tis 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.
- Subjects
0301 basic medicine ,Oncology ,Male ,Colorectal cancer ,humanos ,lcsh:Medicine ,Tumour biomarkers ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Carcinoembryonic antigen ,Neoplasias colorrectales ,supervivencia sin enfermedad ,Neoplasm Metastasis ,lcsh:Science ,metástasis neoplásica ,mediana edad ,MicroARNs ,Multidisciplinary ,biology ,Extracellular vesicle ,Middle Aged ,Bevacizumab ,030220 oncology & carcinogenesis ,Female ,Colorectal Neoplasms ,medicine.drug ,medicine.medical_specialty ,neoplasias colorrectales ,Check Tags::Male [Medical Subject Headings] ,Context (language use) ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::Carcinoembryonic Antigen [Medical Subject Headings] ,Article ,Disease-Free Survival ,03 medical and health sciences ,Extracellular Vesicles ,Internal medicine ,Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings] ,Persons::Persons::Volunteers::Healthy Volunteers [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,medicine ,Biomarkers, Tumor ,Chemotherapy ,Humans ,Progression-free survival ,Liquid biopsy ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings] ,business.industry ,lcsh:R ,Cancer ,Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings] ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,microARN ,medicine.disease ,Vesículas extracelulares ,Chemicals and Drugs::Complex Mixtures::Biological Products [Medical Subject Headings] ,MicroRNAs ,030104 developmental biology ,Check Tags::Female [Medical Subject Headings] ,biology.protein ,lcsh:Q ,Quimioterapia ,business - Abstract
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., Roche Spain, University of Granada (DdMP), Spanish Government REF FPU14/05461
- Published
- 2020