Lipidomics and Transcriptomics Differ Liposarcoma Differentiation Characteristics That Can Be Altered by Pentose Phosphate Pathway Intervention

  • Metabolites. 2022 Dec 7;12(12):1227. doi: 10.3390/metabo12121227.
Zhengqing Song  1 ,  Shuaikang Wang  1 ,  Lili Lu  1 ,  Jingshen Xu  1 ,  Qiwen Zhou  1 ,  Weiqi Lu  1 ,  Hanxing Tong  1 ,  Yong Zhang  1 ,  Wenshuai Liu  1 ,  Zhiming Wang  1 ,  Wei Li  1 ,  Yang You  1 ,  Chenlu Zhang  1 ,  Xi Guo  1 ,  Rongkui Luo  1 ,  Yingyong Hou  1 ,  Chunmeng Wang  2 ,  Yuexiang Wang  3 ,  Lei Sun  1 ,  He Huang  1  4 ,  Yuhong Zhou  1
Affiliations
  • 1. Department 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.
  • 2. Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 3. Institute of Nutritional and Health Science, Chinese Academy of Sciences, Shanghai 200031, China.
  • 4. Shanghai Qi Zhi Institute, Shanghai 200030, China.
PMID: 36557266 DOI: 10.3390/metabo12121227
Abstract

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor's metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

Keywords
adipogenic differentiation; lipidomics; liposarcoma; pentose phosphate pathway; transcriptomics.
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