6533b7d3fe1ef96bd1261420

RESEARCH PRODUCT

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

María Dolores Sanchez-izquierdoElena Blanco-alcainaAndres PovedaAndrea Martínez-martínezAntonio Fernandez-serraSilvia Calabuig-fariñasRaquel López-reigMaria Lopez-alvarezAntonio GutierrezJosé Antonio López-guerreroJosé Antonio López-guerreroAntònia Obrador-heviaRegina AlemanyJavier Martin-brotoIrene Carrasco-garciaDavid S. MouraMarta Ramírez-calvoNadia Hindi

subject

caspase-3Cancer Research<i>let-7e</i>Biologylcsh:RC254-282prognostic 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]microRNAGene expressionmedicine:Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings]Mirna profilingGastrointestinal stromal tumors:Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Paraffin [Medical Subject Headings]GeneACVR1B:Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms Connective and Soft Tissue::Neoplasms Connective Tissue::Gastrointestinal Stromal Tumors [Medical Subject Headings]MicroARNsGiSTTumores del estroma gastrointestinalPronósticoMicroRNAlcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensmedicine.diseasePrognosislet-7e:Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Antisense Elements (Genetics)::RNA Antisense::MicroRNAs [Medical Subject Headings]BiomarcadoresOncologyPrognostic biomarkersCaspase-3<i>miR-550</i>Gene chip analysisCancer research:Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings]Target genesSarcomaGIST

description

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.

10.3390/cancers12102979https://hdl.handle.net/10668/4579