Changes in FXR1 expression after Chemotherapy for Rhabdomyosarcoma

Area of Science:

• Oncology
• Molecular Biology
• Developmental Biology

Background:

• Rhabdomyosarcoma (RMS) originates from aberrant muscle development.
• Fragile-X-Related 1 (FXR1) is crucial for normal myogenesis and was previously found to be highly expressed in RMS.
• This study investigates FXR1 expression in relation to RMS characteristics and treatment outcomes.

Purpose of the Study:

• To explore the expression patterns of FXR1 across diverse rhabdomyosarcoma (RMS) disease characteristics.
• To assess the correlation between FXR1 expression and treatment response in RMS patients.
• To determine the prognostic significance of FXR1 expression in relation to patient survival.

Main Methods:

• Analyzed FXR1 protein expression in 152 RMS patients (diagnosed 1980-2019, age ≤18).
• Categorized patients by tumor histology, PAX/FOXO1 translocation, and vital status.
• Compared FXR1 expression pre- and post-chemotherapy and correlated it with relapse-free (RFS) and overall survival (OS).

Main Results:

• FXR1 demonstrated intense cytosolic expression in undifferentiated rhabdomyoblasts and was universally strong at diagnosis.
• High FXR1 expression at diagnosis correlated with worse RFS in translocation-positive RMS (p=0.0411).
• Survivors with embryonal/translocation-negative RMS showed a significant decrease in FXR1 post-chemotherapy (p<0.001), unlike non-survivors (p=0.8). Alveolar/translocation-positive RMS showed minimal FXR1 change.

Conclusions:

• FXR1 is strongly expressed in RMS at diagnosis, particularly in undifferentiated cells, irrespective of patient or disease characteristics.
• A reduction in FXR1 expression following chemotherapy is linked to improved survival in embryonal and translocation-negative RMS.
• FXR1 expression serves as a potential biomarker for treatment response in specific RMS subtypes.