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Prediction of desmoid tumor progression using miRNA expression profiling
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Journal Article
Prediction of desmoid tumor progression using miRNA expression profiling
2015
Overview
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.
This study was conducted to define the potential predictive and/or prognostic value of a miRNA expression profile of desmoid tumors. The results bring the first demonstration of the prognostic value of miRNA profile in DT. The results were obtained in a cohort of patients included in a clinical phase II trial and validated in an independent cohort. The implication of such a discovery will be important in the management of patients with tumors particularly over‐treated.
Publisher
BlackWell Publishing Ltd
Subject
Abdominal Neoplasms - drug therapy
/ Abdominal Neoplasms - genetics
/ Abdominal Neoplasms - pathology
/ Adult
/ Aged
/ Benzamides - therapeutic use
/ Biomarkers, Tumor - genetics
/ Female
/ Fibromatosis, Aggressive - drug therapy
/ Fibromatosis, Aggressive - genetics
/ Fibromatosis, Aggressive - pathology
/ Fibromatosis, Aggressive - surgery
/ Gene Expression Regulation, Neoplastic
/ Humans
/ imatinib
/ Male
/ miRNA
/ Original
/ Piperazines - therapeutic use
