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Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis

To identify metabolic pathways that were perturbed in pancreatic cancer (PC), we investigated gene‐metabolite networks by integration of metabolomic and transcriptomic. In this research, we undertook the metabolomic study of 43 paired human PC samples, aiming to identify key metabolic alterations in...

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Autores principales: An, Yong, Cai, Huihua, Yang, Yong, Zhang, Yue, Liu, Shengyong, Wu, Xinquan, Duan, Yunfei, Sun, Donglin, Chen, Xuemin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125470/
https://www.ncbi.nlm.nih.gov/pubmed/29987902
http://dx.doi.org/10.1111/cas.13733
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author An, Yong
Cai, Huihua
Yang, Yong
Zhang, Yue
Liu, Shengyong
Wu, Xinquan
Duan, Yunfei
Sun, Donglin
Chen, Xuemin
author_facet An, Yong
Cai, Huihua
Yang, Yong
Zhang, Yue
Liu, Shengyong
Wu, Xinquan
Duan, Yunfei
Sun, Donglin
Chen, Xuemin
author_sort An, Yong
collection PubMed
description To identify metabolic pathways that were perturbed in pancreatic cancer (PC), we investigated gene‐metabolite networks by integration of metabolomic and transcriptomic. In this research, we undertook the metabolomic study of 43 paired human PC samples, aiming to identify key metabolic alterations in PC. We also carried out in vitro experiments to validate that the key metabolite cytidine and its related gene ENTPD8 played an important role in PC cell proliferation. We screened out 13 metabolites differentially expressed in PC tissue (PCT) by liquid chromatography/mass spectrometry analysis on 34 metabolites, and the partial least square discrimination analysis results revealed that 9 metabolites among them were remarkably altered in PCT compared to adjacent noncancerous tissue (variable importance in projection >1, P < .05). Among the 9 metabolites, 7 might be potential biomarkers. The most significantly enriched metabolic pathway was pyrimidine metabolism. We analyzed 351 differentially expressed genes from The Cancer Genome Atlas and intersected them with Kyoto Encyclopedia of Genes and Genomes metabolic pathways. We found that ENTPD8 had a gene‐metabolite association with cytidine in the CTP dephosphorylation pathway. We verified by in vitro experiments that the CTP dephosphorylation pathway was changed in PCT compared with adjacent noncancerous tissue. ENTPD8 was downregulated in PCT, causing a reduction in cytidine formation and hence weakened CTP dephosphorylation in pyrimidine metabolism.
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spelling pubmed-61254702018-09-10 Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis An, Yong Cai, Huihua Yang, Yong Zhang, Yue Liu, Shengyong Wu, Xinquan Duan, Yunfei Sun, Donglin Chen, Xuemin Cancer Sci Original Articles To identify metabolic pathways that were perturbed in pancreatic cancer (PC), we investigated gene‐metabolite networks by integration of metabolomic and transcriptomic. In this research, we undertook the metabolomic study of 43 paired human PC samples, aiming to identify key metabolic alterations in PC. We also carried out in vitro experiments to validate that the key metabolite cytidine and its related gene ENTPD8 played an important role in PC cell proliferation. We screened out 13 metabolites differentially expressed in PC tissue (PCT) by liquid chromatography/mass spectrometry analysis on 34 metabolites, and the partial least square discrimination analysis results revealed that 9 metabolites among them were remarkably altered in PCT compared to adjacent noncancerous tissue (variable importance in projection >1, P < .05). Among the 9 metabolites, 7 might be potential biomarkers. The most significantly enriched metabolic pathway was pyrimidine metabolism. We analyzed 351 differentially expressed genes from The Cancer Genome Atlas and intersected them with Kyoto Encyclopedia of Genes and Genomes metabolic pathways. We found that ENTPD8 had a gene‐metabolite association with cytidine in the CTP dephosphorylation pathway. We verified by in vitro experiments that the CTP dephosphorylation pathway was changed in PCT compared with adjacent noncancerous tissue. ENTPD8 was downregulated in PCT, causing a reduction in cytidine formation and hence weakened CTP dephosphorylation in pyrimidine metabolism. John Wiley and Sons Inc. 2018-09-03 2018-09 /pmc/articles/PMC6125470/ /pubmed/29987902 http://dx.doi.org/10.1111/cas.13733 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
An, Yong
Cai, Huihua
Yang, Yong
Zhang, Yue
Liu, Shengyong
Wu, Xinquan
Duan, Yunfei
Sun, Donglin
Chen, Xuemin
Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title_full Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title_fullStr Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title_full_unstemmed Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title_short Identification of ENTPD8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
title_sort identification of entpd8 and cytidine in pancreatic cancer by metabolomic and transcriptomic conjoint analysis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125470/
https://www.ncbi.nlm.nih.gov/pubmed/29987902
http://dx.doi.org/10.1111/cas.13733
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