July 25, 2023

Signaling pathways in liposarcomas

A broad bioinformatics approach revealed that Hedgehog signaling is upregulated in dedifferentiated liposarcoma, suggesting this pathway may be an early indicator of poor prognosis and a potential therapeutic target.

Liposarcomas — cancers that begin in fat cells — are the most frequently diagnosed soft tissue sarcomas. Clinical prognosis depends on tumor differentiation, with dedifferentiated (less “mature”) liposarcomas often having a worse prognosis due to a higher likelihood of metastasis compared to well-differentiated liposarcomas. 

Julie Rhoades, PhD, associate professor of Medicine in the Division of Clinical Pharmacology, and colleagues sought to identify signaling pathways that contribute to the dedifferentiation process in liposarcoma. 

Using a broad bioinformatics approach, the researchers analyzed previously published data sets (Gene Expression Omnibus and CBioPortal). They reported in the journal Cancers that Hedgehog signaling, a pathway with roles in cell differentiation during embryonic development, is upregulated in dedifferentiated liposarcomas. They identified co-expression signatures linking the transcription factor Gli2 (a mediator of Hedgehog signaling) to increased extracellular matrix protein expression and reduced immune cell infiltration. 

The researchers propose that Hedgehog signaling may influence extracellular matrix deposition and inhibit immune cell infiltration in dedifferentiated liposarcomas, suggesting that this signaling pathway may be an early indicator of poor prognosis and a potential therapeutic target. 

Co-authors of the study include graduate students Erik Beadle and Natalie Bennett. The research was supported by grants from the National Institutes of Health (CA009592, GM007347) and by pilot project funding from the Department of Orthopaedic Surgery at Vanderbilt University Medical Center.