Frontiers in Public Health (Feb 2022)
Metabolic Phenotyping Predicts Gemcitabine and Cisplatin Chemosensitivity in Patients With Cholangiocarcinoma
- Manida Suksawat,
- Manida Suksawat,
- Manida Suksawat,
- Jutarop Phetcharaburanin,
- Jutarop Phetcharaburanin,
- Jutarop Phetcharaburanin,
- Jutarop Phetcharaburanin,
- Poramate Klanrit,
- Poramate Klanrit,
- Poramate Klanrit,
- Nisana Namwat,
- Nisana Namwat,
- Nisana Namwat,
- Narong Khuntikeo,
- Narong Khuntikeo,
- Narong Khuntikeo,
- Attapon Titapun,
- Attapon Titapun,
- Attapon Titapun,
- Apiwat Jarearnrat,
- Apiwat Jarearnrat,
- Apiwat Jarearnrat,
- Vanlakhone Vilayhong,
- Vanlakhone Vilayhong,
- Vanlakhone Vilayhong,
- Prakasit Sa-ngiamwibool,
- Prakasit Sa-ngiamwibool,
- Prakasit Sa-ngiamwibool,
- Anchalee Techasen,
- Anchalee Techasen,
- Anchalee Techasen,
- Arporn Wangwiwatsin,
- Arporn Wangwiwatsin,
- Arporn Wangwiwatsin,
- Arporn Wangwiwatsin,
- Panupong Mahalapbutr,
- Panupong Mahalapbutr,
- Jia V. Li,
- Watcharin Loilome,
- Watcharin Loilome,
- Watcharin Loilome,
- Watcharin Loilome
Affiliations
- Manida Suksawat
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Manida Suksawat
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Manida Suksawat
- Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University, Khon Kaen, Thailand
- Jutarop Phetcharaburanin
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Jutarop Phetcharaburanin
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Jutarop Phetcharaburanin
- Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University, Khon Kaen, Thailand
- Jutarop Phetcharaburanin
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Poramate Klanrit
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Poramate Klanrit
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Poramate Klanrit
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Nisana Namwat
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Nisana Namwat
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Nisana Namwat
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Narong Khuntikeo
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Narong Khuntikeo
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Attapon Titapun
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Attapon Titapun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Attapon Titapun
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Apiwat Jarearnrat
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Apiwat Jarearnrat
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Apiwat Jarearnrat
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Vanlakhone Vilayhong
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Vanlakhone Vilayhong
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Vanlakhone Vilayhong
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Prakasit Sa-ngiamwibool
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Prakasit Sa-ngiamwibool
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Prakasit Sa-ngiamwibool
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Anchalee Techasen
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Anchalee Techasen
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Anchalee Techasen
- Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand
- Arporn Wangwiwatsin
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Arporn Wangwiwatsin
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Arporn Wangwiwatsin
- Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University, Khon Kaen, Thailand
- Arporn Wangwiwatsin
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- Panupong Mahalapbutr
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Panupong Mahalapbutr
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Jia V. Li
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London, United Kingdom
- Watcharin Loilome
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Watcharin Loilome
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
- Watcharin Loilome
- Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University, Khon Kaen, Thailand
- Watcharin Loilome
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand
- DOI
- https://doi.org/10.3389/fpubh.2022.766023
- Journal volume & issue
-
Vol. 10
Abstract
Gemcitabine and cisplatin serve as appropriate treatments for patients with cholangiocarcinoma (CCA). Our previous study using histoculture drug response assay (HDRA), demonstrated individual response patterns to gemcitabine and cisplatin. The current study aimed to identify predictive biomarkers for gemcitabine and cisplatin sensitivity in tissues and sera from patients with CCA using metabolomics. Metabolic signatures of patients with CCA were correlated with their HDRA response patterns. The tissue metabolic signatures of patients with CCA revealed the inversion of the TCA cycle that is evident with increased levels of citrate and amino acid backbones as TCA cycle intermediates, and glucose which corresponds to cancer stem cell (CSC) properties. The protein expression levels of CSC markers were examined on tissues and showed the significantly inverse association with the responses of patients to cisplatin. Moreover, the elevation of ethanol level was observed in gemcitabine- and cisplatin-sensitive group. In serum, a lower level of glucose but a higher level of methylguanidine was observed in the gemcitabine-responders as non-invasive predictive biomarker for gemcitabine sensitivity. Collectively, our findings indicate that these metabolites may serve as the predictive biomarkers in clinical practice which not only predict the chemotherapy response in patients with CCA but also minimize the adverse effect from chemotherapy.
Keywords
- cholangiocarcinoma (CCA)
- gemcitabine
- cisplatin
- nuclear magnetic resonance (NMR) spectroscopy
- predictive biomarker
