Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

• Published in: Frontiers of medicine 2024-04, Vol.18 (2), p.375-393
• Main Authors: Xie, Fu’an, Niu, Yujia, Lian, Lanlan, Wang, Yue, Zhuang, Aobo, Yan, Guangting, Ren, Yantao, Chen, Xiaobing, Xiao, Mengmeng, Li, Xi, Xi, Zhe, Zhang, Gen, Qin, Dongmei, Yang, Kunrong, Zheng, Zhigang, Zhang, Quan, Xia, Xiaogang, Li, Peng, Gu, Lingwei, Wu, Ting, Luo, Chenghua, Lin, Shu-Hai, Li, Wengang
• Format: Article
• Language: English
• Subjects: Medicine; Medicine & Public Health; Research Article
• ISSN: 2095-0217; 2095-0225
• DOI: 10.1007/s11684-023-1020-z

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis ( n = 10), metabolomic analysis ( n = 51), and lipidomic analysis ( n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.