Dynamic metabolic change is indicative of inflammation-induced transformation of hepatic cells |
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| Institution: | 1. Zhongshan Hospital, Medical College of Xiamen University, Xiamen 361004, PR China;2. Department of Basic Medicine, Medical College of Xiamen University/Cancer Research Center of Xiamen University, Xiamen 361102, PR China;3. Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8197, USA;4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6160, USA;1. Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran;2. Clinical Neurology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran;3. Neuroscience Research Centre, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran;1. Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquatic Food Safety, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China;2. Department of Biological Sciences, The University of Texas, El Paso, TX 79968, USA;1. Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China;2. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China;1. Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomas C.P. 11340, Delegación Miguel Hidalgo, México, D.F., Mexico;2. Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu s/n, Esq. Manuel Stampa, Unidad Profesional Adolfo López Mateos, C.P. 07738, Delegación Gustavo A. Madero, México, D.F., Mexico;3. Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom |
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| Abstract: | The observation that prolonged inflammation plays a causative role in cancer development has been well documented. However, an incremental process that leads from healthy to malignant phenotypes has not yet been described. Experimentally induced hepatocellular carcinoma is considered one of the representative laboratory models for studying this process. Hepatic exposure to viral infection or toxic reagents leads to chronic inflammation and gradual transformation into hepatocellular carcinoma. Here we present metabolomic profiles of hepatic cells at different stages during inflammation-induced cellular transformation by N-nitrosodiethylamine. Using gas chromatography–mass spectrometry, we quantitatively assessed the changes in cellular metabolites during the transformation process in hepatitis and liver cirrhosis. Further pathway analysis of the differentially expressed metabolites showed that carbohydrate metabolism and lipid metabolism were greatly altered in hepatitis and liver cirrhosis, respectively. Additionally, the enhanced inflammation in cirrhosis was associated with a shift from carbohydrate metabolism to lipid and amino acid metabolism. Among the differentially expressed metabolites found in diseased mouse livers, d-glucose and d-mannitol showed the most significant changes, highlighting them as potential early-diagnostic biomarkers of hepatocellular carcinoma development. Taken together, these investigations into the dynamic metabolic changes that occur during the precancerous stages of hepatocellular carcinoma add to and refine understanding of how chronic inflammation ultimately leads to cancer. Furthermore, the findings set the stage for identifying metabolites that may serve as early-diagnostic indicators of these unfolding events. |
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| Keywords: | Hepatocellular carcinoma Chronic inflammation Metabolomics Biomarker Mass spectrometry |
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