Integration of global metabolomics and lipidomics approaches reveals the molecular mechanisms and the potential biomarkers for postoperative recurrence in early-stage cholangiocarcinoma

Cancer & Metabolism

Attapol Titapun¹  Apiwat Jarearnrat¹  Narong Khuntikeo¹  Poramate Klanrit²  Panupong Mahalapbutr²  Sureerat Padthaisong²  Arporn Wangwiwatsin²  Watcharin Loilome²  Jutarop Phetcharaburanin²  Nisana Namwat²  Jia V. Li³ 

[1] Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University;Department of Biochemistry, Faculty of Medicine, Khon Kaen University;Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London;

关键词: Cholangiocarcinoma;    Cancer recurrence;    Metabolomics;    Lipidomics;    Biomarker;   

DOI  :  10.1186/s40170-021-00266-5

来源: DOAJ

【 摘 要 】

Abstract Background Cholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcomes. Methods We performed 1H-NMR and UPLC-MS-based metabolomics on the CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarker identification. Results At an early stage, the metabolites involved in energy metabolisms, such as pyruvate metabolism, and the TCA cycle, are downregulated, while most lipids, including TGs, PCs, PEs, and PAs, are upregulated in recurrence patients. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. In addition, the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. We also found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate, and TGs have good predictive values for CCA recurrence. Conclusion Our study demonstrates the possible molecular mechanisms underlying CCA recurrence, and these may associate with the existence of CSCs. The metabolic change involved in the recurrence pathway might be used to determine biomarkers for predicting CCA recurrence.

【 授权许可】

Unknown