title: Prediction of desmoid tumor progression using miRNA expression profiling.
abstract: 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.
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Dufresne
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Paturel
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alberti
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.
authors.forename: Heloise
authors.initials: H
authors.lastname: Philippon
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Duc
authors.affiliation: Department of Pathology, Leon Berard Cancer Center, Lyon, France.
authors.forename: Anne-Valerie
authors.initials: AV
authors.lastname: Decouvelaere
authors.affiliation: Department of Medical Oncology, Leon Berard Cancer Center, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cassier
authors.affiliation: Team 11 of the Cancer Research Center of Lyon, Institute of Health and Medical Research (INSERM U1052-CNRS 5286), Lyon, France.|Department of Medical Oncology, Leon Berard Cancer Center, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D018222:Desmoid Tumors / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Aggressive fibromatosis; desmoid tumor; imatinib; miRNA; prognosis