Comprehensive Metaboproteomics of Burkitt's and Diffuse Large B-Cell Lymphoma Cell Lines and Primary Tumor Tissues Reveals Distinct Differences in Pyruvate Content and Metabolism

Schwarzfischer, Philipp and Reinders, Joerg and Dettmer, Katja and Kleo, Karsten and Dimitrova, Lora and Hummel, Michael and Feist, Maren and Kube, Dieter and Szczepanowski, Monika and Klapper, Wolfram and Taruttis, Franziska and Engelmann, Julia C. and Spang, Rainer and Gronwald, Wolfram and Oefner, Peter J. (2017) Comprehensive Metaboproteomics of Burkitt's and Diffuse Large B-Cell Lymphoma Cell Lines and Primary Tumor Tissues Reveals Distinct Differences in Pyruvate Content and Metabolism. JOURNAL OF PROTEOME RESEARCH, 16 (3). 1105-+. ISSN 1535-3893, 1535-3907

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Abstract

Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are pathologically and clinically distinct subtypes of aggressive non-Hodgkin B-cell lymphoma. To learn more about their biology, we employed metabolomic and proteomic methods to study both established cell lines as well as cryopreserved and formalin-fixed paraffin-embedded (FFPE) tissue sections of BL and DLBCL. Strikingly, NMR analyses revealed DLBCL cell lines to produce and secrete significantly (P-adj = 1.72 X 10(-22)) more pyruvic acid than BL cell lines. This finding could be reproduced by targeted GC/MS analyses of cryopreserved tissue sections of BL and DLBCL cases. Enrichment analysis of an overlapping set of N = 2315 proteins, that had been quantified by nanoLC-SWATH-MS in BL and DLBCL cultured cells and cryosections, supported the observed difference in pyruvic acid content, as glycolysis and pyruvate metabolism were downregulated, while one-carbon metabolism was upregulated in BL compared to DLBCL. Furthermore, 92.1% of the overlapping significant proteins showed the same direction of regulation in cryopreserved and FFPE material. Proteome data are available via ProteomeXchange with identifier PXD004936.

Item Type: Article
Uncontrolled Keywords: PROTEIN EXPRESSION PROFILES; NEXT-GENERATION; CANCER; SIGNATURES; QUANTIFICATION; CLASSIFICATION; METABOLOMICS; DIAGNOSIS; SUBTYPES; BIOLOGY; metabolomics; proteomics; FFPE; BL; DLBCL; NMR; SWATH-MS; pyruvate
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:01
Last Modified: 20 Feb 2019 10:43
URI: https://pred.uni-regensburg.de/id/eprint/308

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