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Lipidomics and Transcriptomics Differ Liposarcoma Differentiation Characteristics That Can Be Altered by Pentose
Zhengqing Song1, Shuaikang Wang1, Lili Lu1
1Department of Medical Oncology, Biotherapy Center, Department of General Surgery, Department of Pathology, Zhongshan Hospital, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Developmental Biology and Molecular Medicine, Fudan University, Shanghai 200032, China.
This study reveals distinct lipid profiles in well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS), identifying key metabolic differences. These findings highlight potential therapeutic targets for liposarcoma (LPS) treatment.
Area of Science:
- Oncology
- Metabolomics
- Molecular Biology
Background:
- Liposarcoma (LPS) is a rare cancer originating from fat cells, with subtypes like well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma exhibiting different aggressiveness.
- Understanding the metabolic differences between WDLPS and DDLPS is crucial for developing targeted therapies, as DDLPS is more prone to metastasis.
Purpose of the Study:
- To investigate and compare the distinct lipid alterations between WDLPS and DDLPS subtypes.
- To explore the role of metabolic pathways, specifically the pentose phosphate pathway (PPP), in liposarcoma development and differentiation.
Main Methods:
- Untargeted lipidomic analysis using high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) on WDLPS and DDLPS patient tissues.
- Transcriptomic analysis to compare LPS subtypes with stromal vascular fractions at various differentiation stages.
- Ex vivo treatment of a liposarcoma cell line (LPS853) with a PPP inhibitor (6-aminonicotinamide).
Main Results:
- Lipidomic analysis revealed upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and upregulated triglycerides and diglycerides in WDLPS.
- Transcriptomic data indicated that the pentose phosphate pathway (PPP) was upregulated in WDLPS compared to DDLPS.
- Inhibition of the PPP in the LPS853 cell line significantly promoted proliferation and invasion, suggesting its role in LPS development.
Conclusions:
- This study provides the first comprehensive description of altered lipid profiles in WDLPS and DDLPS, differentiating their metabolic characteristics.
- The findings suggest that distinct lipid profiles reflect the different differentiation stages of WDLPS and DDLPS.
- The pentose phosphate pathway (PPP) emerges as a potential metabolic target for liposarcoma treatment.
