Piotr Popławski1, Takayuki Tohge2, Joanna Bogusławska1, Beata Rybicka1, Zbigniew Tański3, Victor Treviño4, Alisdair R Fernie2, Agnieszka Piekiełko-Witkowska5. 1. Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Warsaw, Poland. 2. Max-Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany. 3. Masovian Specialist Hospital in Ostroleka, Ostroleka, Poland. 4. Cátedra de Bioinformática, Tecnológico de Monterrey, Monterrey, Nuevo León, Mexico. 5. Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Warsaw, Poland. Electronic address: apiekielko@cmkp.edu.pl.
Abstract
PURPOSE: Cellular metabolism of renal cell carcinoma (RCC) tumors is disturbed. The clinical significance of these alterations is weakly understood. We aimed to find if changes in metabolic pathways contribute to survival of RCC patients. MATERIAL AND METHODS: 35 RCC tumors and matched controls were used for metabolite profiling using gas chromatography-mass spectrometry and transcriptomic analysis with qPCR-arrays targeting the expression of 93 metabolic genes. The clinical significance of obtained data was validated on independent cohort of 468 RCC patients with median follow-up of 43.22months. RESULTS: The levels of 31 metabolites were statistically significantly changed in RCC tumors compared with controls. The top altered metabolites included beta-alanine (+4.2-fold), glucose (+3.4-fold), succinate (-11.0-fold), myo-inositol (-4.6-fold), adenine (-4.2-fold), uracil (-3.7-fold), and hypoxanthine (-3.0-fold). These disturbances were associated with altered expression of 53 metabolic genes. ROC curve analysis revealed that the top metabolites discriminating between tumor and control samples included succinate (AUC=0.91), adenine (AUC=0.89), myo-inositol (AUC=0.87), hypoxanthine (AUC=0.85), urea (AUC=0.85), and beta-alanine (AUC=0.85). Poor survival of RCC patients correlated (p<0.0001) with altered expression of genes involved in metabolism of succinate (HR=2.7), purines (HR=2.4), glucose (HR=2.4), beta-alanine (HR=2.5), and myo-inositol (HR=1.9). CONCLUSIONS: We found that changes in metabolism of succinate, beta-alanine, purines, glucose and myo-inositol correlate with poor survival of RCC patients.
PURPOSE: Cellular metabolism of renal cell carcinoma (RCC) tumors is disturbed. The clinical significance of these alterations is weakly understood. We aimed to find if changes in metabolic pathways contribute to survival of RCCpatients. MATERIAL AND METHODS: 35 RCC tumors and matched controls were used for metabolite profiling using gas chromatography-mass spectrometry and transcriptomic analysis with qPCR-arrays targeting the expression of 93 metabolic genes. The clinical significance of obtained data was validated on independent cohort of 468 RCCpatients with median follow-up of 43.22months. RESULTS: The levels of 31 metabolites were statistically significantly changed in RCC tumors compared with controls. The top altered metabolites included beta-alanine (+4.2-fold), glucose (+3.4-fold), succinate (-11.0-fold), myo-inositol (-4.6-fold), adenine (-4.2-fold), uracil (-3.7-fold), and hypoxanthine (-3.0-fold). These disturbances were associated with altered expression of 53 metabolic genes. ROC curve analysis revealed that the top metabolites discriminating between tumor and control samples included succinate (AUC=0.91), adenine (AUC=0.89), myo-inositol (AUC=0.87), hypoxanthine (AUC=0.85), urea (AUC=0.85), and beta-alanine (AUC=0.85). Poor survival of RCCpatients correlated (p<0.0001) with altered expression of genes involved in metabolism of succinate (HR=2.7), purines (HR=2.4), glucose (HR=2.4), beta-alanine (HR=2.5), and myo-inositol (HR=1.9). CONCLUSIONS: We found that changes in metabolism of succinate, beta-alanine, purines, glucose and myo-inositol correlate with poor survival of RCCpatients.
Authors: Piotr Popławski; Jacek R Wiśniewski; Eddy Rijntjes; Keith Richards; Beata Rybicka; Josef Köhrle; Agnieszka Piekiełko-Witkowska Journal: PLoS One Date: 2017-12-22 Impact factor: 3.240
Authors: Filipa Amaro; Joana Pinto; Sílvia Rocha; Ana Margarida Araújo; Vera Miranda-Gonçalves; Carmen Jerónimo; Rui Henrique; Maria de Lourdes Bastos; Márcia Carvalho; Paula Guedes de Pinho Journal: Metabolites Date: 2020-04-27
Authors: Joanna Nizioł; Krzysztof Ossoliński; Brian P Tripet; Valérie Copié; Adrian Arendowski; Tomasz Ruman Journal: Anal Bioanal Chem Date: 2020-07-13 Impact factor: 4.142
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