Metabolic Phenotyping Predicts Gemcitabine and Cisplatin Chemosensitivity in Patients With Cholangiocarcinoma

Frontiers in Public Health

article

Manida Suksawat¹  Jutarop Phetcharaburanin¹  Poramate Klanrit¹  Nisana Namwat¹  Narong Khuntikeo²  Attapon Titapun²  Apiwat Jarearnrat²  Vanlakhone Vilayhong²  Prakasit Sa-ngiamwibool²  Anchalee Techasen²  Arporn Wangwiwatsin¹  Panupong Mahalapbutr¹  Jia V. Li⁸  Watcharin Loilome¹ 

[1] Department of Biochemistry, Faculty of Medicine, Khon Kaen University;Cholangiocarcinoma Research Institute, Khon Kaen University;Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University;Cholangiocarcinoma Screening and Care Program ,(CASCAP), Khon Kaen University;Department of Surgery, Faculty of Medicine, Khon Kaen University;Department of Pathology, Faculty of Medicine, Khon Kaen University;Faculty of Associated Medical Sciences, Khon Kaen University;Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus

关键词: cholangiocarcinoma (CCA);    gemcitabine;    cisplatin;    nuclear magnetic resonance (NMR) spectroscopy;    predictive biomarker;   

DOI  :  10.3389/fpubh.2022.766023

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY