Prediction of desmoid tumor progression using miRNA expression profiling

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Desmoid tumors are rare, aggressive connective tissue neoplasms with unpredictable behavior.
• Current treatment strategies lack precise predictive biomarkers for patient stratification.

Purpose of the Study:

• To investigate the potential of microRNA (miRNA) expression profiling for predicting desmoid tumor behavior and patient outcomes.
• To identify miRNA signatures associated with treatment response and prognosis in desmoid tumor patients.

Main Methods:

• miRNA profiling was performed on two cohorts: a 26-patient Desminib phase II trial cohort and a 15-patient independent validation cohort.
• Unsupervised hierarchical clustering was used to identify patient groups based on miRNA expression.
• Supervised analysis was employed to identify differentially expressed miRNAs between progressive and non-progressive patient groups.

Main Results:

• Hierarchical clustering identified two distinct patient groups (A and B) in both cohorts, differing in prior treatment lines.
• Group B exhibited a longer time to progression after imatinib discontinuation compared to Group A.
• Fifteen differentially expressed miRNAs were identified between the groups, targeting over 3000 genes, including key regulators like BCL2, CDK6, and VEGFA.
• These miRNA expression patterns were validated in the independent cohort, showing statistically different times to recurrence (28.8 vs 68.8 months).

Conclusions:

• miRNA expression profiling demonstrates prognostic value in desmoid tumors.
• The identified miRNA signature can differentiate patient groups with distinct clinical trajectories.
• These findings may inform personalized patient management, potentially identifying individuals who may not benefit from surgery and could be monitored non-invasively.