1. Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study
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María Dolores Sanchez-Izquierdo, Elena Blanco-Alcaina, Andres Poveda, Andrea Martínez-Martínez, Antonio Fernandez-Serra, Silvia Calabuig-Fariñas, Raquel López-Reig, Maria Lopez-Alvarez, Antonio Gutierrez, José Antonio López-Guerrero, Antònia Obrador-Hevia, Regina Alemany, Javier Martin-Broto, Irene Carrasco-Garcia, David S. Moura, Marta Ramírez-Calvo, Nadia Hindi, [Fernandez-Serra,A, Martínez-Martínez,A, Ramírez-Calvo,M, López-Reig,R, Lopez-Guerrero,JA] Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. [Moura,DS, Lopez-Alvarez,M, Carrasco-Garcia,I, Blanco-Alcaina,E, Hindi,N, Martin-Broto,J] Institute of Biomedicine of Sevilla (IBIS, HUVR, CSIC, Universidad de Sevilla), Sevilla, Spain. [Sanchez-Izquierdo,MD] Instituto de Investigación Sanitaria La Fe, Valencia, Spain. [Calabuig-Fariñas,S] Molecular Oncology Laboratory, Fundación Investigación, Hospital General Universitario de Valencia, Valencia, Spain. [Calabuig-Fariñas,S] Centro de Investigación Biomédica en Red de Cáncer (CIBEROnc), Madrid, Spain. [Calabuig-Fariñas,S] Department of Pathology, Universitat de València, Valencia, Spain. [Carrasco-Garcia,I, Martin-Broto,J] Medical Oncology Department, University Hospital Virgen del Rocio, Sevilla, Spain. [Obrador-Hevia,A] Group of Advanced Therapies and Biomarkers in Clinical Oncology, Institut d’Investigació Sanitària de les Illes Balears (IdISBa-IUNICS), Palma de Mallorca, Spain. [Obrador-Hevia,A] Sequencing Unit, University Hospital Son Espases, Palma de Mallorca, Spain. [Alemany,R] Department of Biology, Balearic Islands University, Palma de Mallorca, Spain. [Gutierrez,A] Hematology Department, University Hospital Son Espases, Mallorca, Spain. [Poveda,A] Medical Oncology Department, Fundación Instituto Valenciano de Oncología, Valencia, Spain. [Lopez-Guerrero,JA] Department of Basic Medical Sciences, School of Medicine, Catholic University of Valencia ‘San Vicente Martir’, Valencia, Spain., The project was funded by the Instituto de Salud Carlos III (ISCIII (Carlos III Health Institute))-Fondo Europeo de Desarrollo Regional, FEDER (European Regional Development Fund (ERDF)), through a public competitive call (project reference PI15/01254, principal investigator Javier Martín Broto) and by the Consejería de la Salud-Junta de Andalucia–(Health Council–Regional Government of Andalusia)-Proyectos de investigación coordinados 2016, through a competitive public call (project reference PC-0537-2016-0537, and principal investigator Nadia Hindi).
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caspase-3 ,Cancer Research ,let-7e ,Biology ,lcsh:RC254-282 ,prognostic biomarkers ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings] ,miR-550 ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Endopeptidases::Cysteine Endopeptidases::Caspases::Caspases, Effector::Caspase 3 [Medical Subject Headings] ,microRNA ,Gene expression ,medicine ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,Mirna profiling ,Gastrointestinal stromal tumors ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Paraffin [Medical Subject Headings] ,Gene ,ACVR1B ,Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Connective Tissue::Gastrointestinal Stromal Tumors [Medical Subject Headings] ,MicroARNs ,GiST ,Tumores del estroma gastrointestinal ,Pronóstico ,MicroRNA ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Prognosis ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,Biomarcadores ,Oncology ,Prognostic biomarkers ,Caspase-3 ,Gene chip analysis ,Cancer research ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,Target genes ,Sarcoma ,GIST - Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were correlated with relapse-free survival and overall survival. In the discovery set, 39 miRNAs were significantly deregulated, let-7e and miR-550 being the most underexpressed and overexpressed miRNAs in the relapsed group, respectively. In the expansion set, the underexpression of let-7e or the overexpression of 4 of its target genes (ACVR1B, CASP3, COL3A1, and COL5A2) were statistically associated with worse relapse-free survival. The expression of let-7e and 4 of its target genes are potential prognostic biomarkers in high-risk localized intestinal GIST. The expression of these genes is a potential molecular tool useful for a more accurate prognosis in this subset of GIST patients.
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- 2020