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Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early an...

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Autores principales: Bai, Changsen, Wang, Hailong, Dong, Dong, Li, Tong, Yu, Zhi, Guo, Junfei, Zhou, Wei, Li, Ding, Yan, Ruochen, Wang, Liyan, Wang, Zhaosong, Li, Yueguo, Ren, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047217/
https://www.ncbi.nlm.nih.gov/pubmed/33869206
http://dx.doi.org/10.3389/fcell.2021.650748
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author Bai, Changsen
Wang, Hailong
Dong, Dong
Li, Tong
Yu, Zhi
Guo, Junfei
Zhou, Wei
Li, Ding
Yan, Ruochen
Wang, Liyan
Wang, Zhaosong
Li, Yueguo
Ren, Li
author_facet Bai, Changsen
Wang, Hailong
Dong, Dong
Li, Tong
Yu, Zhi
Guo, Junfei
Zhou, Wei
Li, Ding
Yan, Ruochen
Wang, Liyan
Wang, Zhaosong
Li, Yueguo
Ren, Li
author_sort Bai, Changsen
collection PubMed
description Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis.
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spelling pubmed-80472172021-04-16 Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma Bai, Changsen Wang, Hailong Dong, Dong Li, Tong Yu, Zhi Guo, Junfei Zhou, Wei Li, Ding Yan, Ruochen Wang, Liyan Wang, Zhaosong Li, Yueguo Ren, Li Front Cell Dev Biol Cell and Developmental Biology Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis. Frontiers Media S.A. 2021-04-01 /pmc/articles/PMC8047217/ /pubmed/33869206 http://dx.doi.org/10.3389/fcell.2021.650748 Text en Copyright © 2021 Bai, Wang, Dong, Li, Yu, Guo, Zhou, Li, Yan, Wang, Wang, Li and Ren. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bai, Changsen
Wang, Hailong
Dong, Dong
Li, Tong
Yu, Zhi
Guo, Junfei
Zhou, Wei
Li, Ding
Yan, Ruochen
Wang, Liyan
Wang, Zhaosong
Li, Yueguo
Ren, Li
Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title_full Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title_fullStr Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title_full_unstemmed Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title_short Urea as a By-Product of Ammonia Metabolism Can Be a Potential Serum Biomarker of Hepatocellular Carcinoma
title_sort urea as a by-product of ammonia metabolism can be a potential serum biomarker of hepatocellular carcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047217/
https://www.ncbi.nlm.nih.gov/pubmed/33869206
http://dx.doi.org/10.3389/fcell.2021.650748
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