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

Abstract

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.

Keywords

RLPS / proteomics / metabolomics / lipidomics / metabolism

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Acknowledgements

We thank Haiping Zheng at the Central laboratory, School of Medicine, Xiamen University for providing scientific and technical support. We also thank LetPub for its linguistic assistance during the preparation of this manuscript.

This research was 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.), 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), and Natural Science Foundation of Fujian Province (No. 2021J01123522 to Zhigang Zheng).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-023-1020-z and is accessible for authorized users.

Compliance with ethics guidelines

Fu’an Xie, Yujia Niu, Lanlan Lian, Yue Wang, Aobo Zhuang, Guangting Yan, Yantao Ren, Xiaobing Chen, Mengmeng Xiao, Xi Li, Zhe Xi, Gen Zhang, Dongmei Qin, Kunrong Yang, Zhigang Zheng, Quan Zhang, Xiaogang Xia, Peng Li, Lingwei Gu, Ting Wu, Chenghua Luo, Shu-Hai Lin, and Wengang Li declare no conflict of interest associated with this publication.

The study was approved by the ethics committee of all participating institutions, including the Xiang’an Hospital of Xiamen University (No. XAHLL2021024) and Peking University International Hospital (No. WA2020RW29). The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. We obtained written informed consent from all participants, except for those we could not contact due to lack of follow-up. In these cases, the institutional review boards at each participating institution granted permission for existing tissue samples to be used for research purposes.

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