Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer

Maosen Huang; Yancen Wu; Linyao Cheng; Lihua Fu; Haochao Yan; Haiming Ru; Xianwei Mo; Linhai Yan; Zijie Su

doi:10.3389/fimmu.2023.1179699

Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer

Front Immunol. 2023 Jul 5:14:1179699. doi: 10.3389/fimmu.2023.1179699. eCollection 2023.

Authors

Maosen Huang¹, Yancen Wu¹, Linyao Cheng¹, Lihua Fu¹, Haochao Yan¹, Haiming Ru^{1

2}, Xianwei Mo^{1

2}, Linhai Yan^{1

2}, Zijie Su^{1

3}

Affiliations

¹ Guangxi Clinical Research Center for Colorectal Cancer, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
² Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.
³ Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, China.

Abstract

Background: Glucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis.

Methods: PET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis.

Results: The glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer.

Conclusions: GMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets.

Keywords: colorectal cancer; glucose metabolic reprogramming; immunology; metastasis; multi-omics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / pathology
Glucose
Humans
Multiomics
Positron Emission Tomography Computed Tomography*
Proteomics

Substances

Glucose

Grants and funding

This research was partially supported by Natural Science Foundation of Guangxi (2022GXNSFAA035636), Natural Science Foundation of Guangxi (2023GXNSFDA026032) and National Natural Science Foundation of China (82160495).