Prediction of desmoid tumor progression using miRNA expression profiling
| Autor: | Philippe A. Cassier, Marie Paturel, Armelle Dufresne, Jean-Yves Blay, Anne-Valérie Decouvelaere, Laurent Alberti, Heloise Philippon, Adeline Duc |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Cancer Research desmoid tumor Aggressive fibromatosis Bioinformatics Piperazines Young Adult medicine Biomarkers Tumor PTEN Humans miRNA Aged Retrospective Studies biology business.industry Gene Expression Profiling Retrospective cohort study Imatinib General Medicine Original Articles Middle Aged medicine.disease Prognosis Discontinuation Gene expression profiling Gene Expression Regulation Neoplastic Fibromatosis Aggressive MicroRNAs Logistic Models Pyrimidines Oncology imatinib Tumor progression Abdominal Neoplasms Cohort Benzamides biology.protein Imatinib Mesylate Female business medicine.drug |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | Desmoid tumor is a rare connective tissue tumor with locoregional aggressiveness but unpredictable behavior. The miRNA profile was ascertained for 26 patients included in the Desminib phase II trial and an independent validation cohort of 15 patients. Predictive and prognostic supervised analysis on the Desminib cohort failed to identify miRNAs differentially expressed between progressive and non-progressive patients under imatinib treatment or between progressive and non-progressive patients after discontinuation of imatinib. However, an unsupervised hierarchical clustering of the Desminib cohort identified two groups (A and B) of 13 patients each, where only the number of previous lines of treatment before inclusion in the study differed significantly between the two groups. Time to progression after discontinuation of imatinib was longer in group B than in group A. Fifteen miRNAs were highly statistically differentially expressed between groups A and B, targeting more than 3000 genes, including AGO1, BCL2, CDK6, SMAD4, PTEN, CCND1, VEGFA, and RB1. These results were confirmed in the independent validation cohort: hierarchical clustering of these 15 miRNAs identified two groups, in which time to recurrence was statistically different (28.8 months vs 68.8 months). These results provide the first indication of the prognostic value of miRNA expression profiling with a possible direct impact on patient management. A more precise miRNA signature must now be determined to select patients who would not benefit from surgical resection of their tumor and who ought to be monitored without treatment. |
| Databáze: | OpenAIRE |
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