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A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates

Uric acid (UA) is the end product of the catabolism of purines, and its serum levels are commonly increased in cancer patients. We aimed to explore the transcriptional regulation of tumour uricogenesis in human tumours, and relate uricogenesis with tumour pathological and pharmacological findings. U...

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Autores principales: Saidak, Zuzana, Louandre, Christophe, Dahmani, Samy, Sauzay, Chloé, Guedda, Sara, Chauffert, Bruno, Chatelain, Denis, Ceballos-Picot, Irene, Galmiche, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146287/
https://www.ncbi.nlm.nih.gov/pubmed/30104401
http://dx.doi.org/10.1042/BSR20171716
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author Saidak, Zuzana
Louandre, Christophe
Dahmani, Samy
Sauzay, Chloé
Guedda, Sara
Chauffert, Bruno
Chatelain, Denis
Ceballos-Picot, Irene
Galmiche, Antoine
author_facet Saidak, Zuzana
Louandre, Christophe
Dahmani, Samy
Sauzay, Chloé
Guedda, Sara
Chauffert, Bruno
Chatelain, Denis
Ceballos-Picot, Irene
Galmiche, Antoine
author_sort Saidak, Zuzana
collection PubMed
description Uric acid (UA) is the end product of the catabolism of purines, and its serum levels are commonly increased in cancer patients. We aimed to explore the transcriptional regulation of tumour uricogenesis in human tumours, and relate uricogenesis with tumour pathological and pharmacological findings. Using data from The Cancer Genome Atlas (TCGA), we analysed the expression levels of xanthine dehydrogenase (XDH) and adenine phosphoribosyltransferase (APRT), two key enzymes in UA production and the purine salvage pathway, respectively. We found large differences between tumour types and individual tumours in their expression of XDH and APRT. Variations in locus-specific DNA methylation and gene copy number correlated with the expression levels of XDH and APRT in human tumours respectively. We explored the consequences of this differential regulation of uricogenesis. Tumours with high levels of XDH mRNA were characterised by higher expression of several genes encoding pro-inflammatory and immune cytokines, and increased levels of tumour infiltration with immune cells. Finally, we studied cancer drug sensitivity using data from the National Cancer Institute-60 (NCI-60) database. A specific correlation was found between the expression levels of APRT and cell sensitivity to the chemotherapeutic agent 5-fluorouracil (5-FU). Our findings underline the existence of great differences in uricogenesis between different types of human tumours. The study of uricogenesis offers promising perspectives for the identification of clinically relevant molecular biomarkers and for tumour stratification in the therapeutic context.
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spelling pubmed-61462872018-09-25 A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates Saidak, Zuzana Louandre, Christophe Dahmani, Samy Sauzay, Chloé Guedda, Sara Chauffert, Bruno Chatelain, Denis Ceballos-Picot, Irene Galmiche, Antoine Biosci Rep Research Articles Uric acid (UA) is the end product of the catabolism of purines, and its serum levels are commonly increased in cancer patients. We aimed to explore the transcriptional regulation of tumour uricogenesis in human tumours, and relate uricogenesis with tumour pathological and pharmacological findings. Using data from The Cancer Genome Atlas (TCGA), we analysed the expression levels of xanthine dehydrogenase (XDH) and adenine phosphoribosyltransferase (APRT), two key enzymes in UA production and the purine salvage pathway, respectively. We found large differences between tumour types and individual tumours in their expression of XDH and APRT. Variations in locus-specific DNA methylation and gene copy number correlated with the expression levels of XDH and APRT in human tumours respectively. We explored the consequences of this differential regulation of uricogenesis. Tumours with high levels of XDH mRNA were characterised by higher expression of several genes encoding pro-inflammatory and immune cytokines, and increased levels of tumour infiltration with immune cells. Finally, we studied cancer drug sensitivity using data from the National Cancer Institute-60 (NCI-60) database. A specific correlation was found between the expression levels of APRT and cell sensitivity to the chemotherapeutic agent 5-fluorouracil (5-FU). Our findings underline the existence of great differences in uricogenesis between different types of human tumours. The study of uricogenesis offers promising perspectives for the identification of clinically relevant molecular biomarkers and for tumour stratification in the therapeutic context. Portland Press Ltd. 2018-09-19 /pmc/articles/PMC6146287/ /pubmed/30104401 http://dx.doi.org/10.1042/BSR20171716 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Saidak, Zuzana
Louandre, Christophe
Dahmani, Samy
Sauzay, Chloé
Guedda, Sara
Chauffert, Bruno
Chatelain, Denis
Ceballos-Picot, Irene
Galmiche, Antoine
A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title_full A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title_fullStr A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title_full_unstemmed A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title_short A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
title_sort pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146287/
https://www.ncbi.nlm.nih.gov/pubmed/30104401
http://dx.doi.org/10.1042/BSR20171716
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