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Systematic analyses of glutamine and glutamate metabolisms across different cancer types

摘要Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types. Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tis-sues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues. Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made: (1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer; (2) glutamine is generally not involved in ATP production in cancer; (3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and (5) glutamate does not contribute to serine synthesis except for bladder cancer. Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected meta-bolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic devel-opment targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.

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作者单位 College of Computer Science and Technology,Jilin University,Chang-chun 130012,Jilin,P.R.China [1] College of Computer Science and Technology,Jilin University,Chang-chun 130012,Jilin,P.R.China;Computational Systems Biology Lab,Department of Biochemistry and Molecular Biology and Institute of Bioinfor-matics,University of Georgia,120 E Green St,Athens,GA 30602,USA [2] Computational Systems Biology Lab,Department of Biochemistry and Molecular Biology and Institute of Bioinfor-matics,University of Georgia,120 E Green St,Athens,GA 30602,USA [3] The First Hospital,Jilin University,Chang-chun 130012,Jilin,P.R.China;Computational Systems Biology Lab,Department of Biochemistry and Molecular Biology and Institute of Bioinfor-matics,University of Georgia,120 E Green St,Athens,GA 30602,USA [4] College of Computer Science and Technology,Jilin University,Chang-chun 130012,Jilin,P.R.China;College of Public Health,Jilin University,Changchun 130012,Jilin,P.R.China;Computational Systems Biology Lab,Department of Biochemistry and Molecular Biology and Institute of Bioinfor-matics,University of Georgia,120 E Green St,Athens,GA 30602,USA [5]
栏目名称 Original Article
DOI 10.1186/s40880-017-0255-y
发布时间 2018-03-13
基金项目
Georgia Research Alliance and the National Natural Science Foundation of China the Science-Technology Development Project from Jilin Province
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