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 remaine...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.展开更多
基金funded by grants from the National Natural Science Foundation of China(No.82272935 to Wengang Li.,Nos.91957120 and 21974114 to Shuhai Lin.)the Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University(No.PM20180917008 to Wengang Li.)+3 种基金Joint laboratory of School of Medicine,Xiamen University-Shanghai Jiangxia Blood Technology Co.Ltd.(No.XDHT2020010C to Wengang Lin and Ye Shen.)the Fundamental Research Funds for the Central Universities(No.20720210001 to Shuhai Lin.)Major Science and Technology Special Project of Fujian Province(No.2022YZ036012 to Shuhai Lin)Natural Science Foundation of Fujian Province(No.2021J01123522 to Zhigang Zheng).
文摘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.
