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Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development

The development of liver cancer would undergo a sequential progression from chronic inflammatory liver disease, cirrhosis to neoplasia. During these pathophysiological changes, abnormal liver microenvironment might induce the hepatocytes to die, abnormally proliferate and initiate cancer stem cells....

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Autores principales: Sun, Lichao, Guo, Chunguang, Burnett, Joseph, Pan, Jian, Yang, Zhihua, Ran, Yuliang, Sun, Duxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264046/
https://www.ncbi.nlm.nih.gov/pubmed/28123604
http://dx.doi.org/10.7150/jca.17060
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author Sun, Lichao
Guo, Chunguang
Burnett, Joseph
Pan, Jian
Yang, Zhihua
Ran, Yuliang
Sun, Duxin
author_facet Sun, Lichao
Guo, Chunguang
Burnett, Joseph
Pan, Jian
Yang, Zhihua
Ran, Yuliang
Sun, Duxin
author_sort Sun, Lichao
collection PubMed
description The development of liver cancer would undergo a sequential progression from chronic inflammatory liver disease, cirrhosis to neoplasia. During these pathophysiological changes, abnormal liver microenvironment might induce the hepatocytes to die, abnormally proliferate and initiate cancer stem cells. Metallocarboxypeptidases (MCPs) involved in multiple biological functions including inflammation, fibrosis and stem cell niche formation. This study aimed to evaluate the expression of carboxypeptidase 4 (CPA4) in hepatitis, liver cirrhosis and liver cancer tissues, and revealed its clinical significance in liver cancer progression. We firstly found that the CPA4 levels in tissues were significantly higher in liver cancer patients than those in other three groups. Then, elevated levels of CPA4 was observed in 57/100 (57%) liver cancer samples, and significantly correlated with Grade and Stage. We also identified a significant positive correlation between aberrant elevation of CPA4 and overexpression of stem cell markers including CD90, AFP and CD34 with follow-up data (n=100). Further Kaplan-Meier analysis confirmed that high levels of CPA4 and CD90 were significant predictors of poor overall survival. Multivariate Cox regression model showed that CPA4 was an independent prognostic factor for patients with liver cancer. This study demonstrated for the first time that high CPA4 expression was closely correlated with hepatocarcinogenesis, and might be used as an independent poor prognostic factor in liver cancer.
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spelling pubmed-52640462017-01-25 Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development Sun, Lichao Guo, Chunguang Burnett, Joseph Pan, Jian Yang, Zhihua Ran, Yuliang Sun, Duxin J Cancer Research Paper The development of liver cancer would undergo a sequential progression from chronic inflammatory liver disease, cirrhosis to neoplasia. During these pathophysiological changes, abnormal liver microenvironment might induce the hepatocytes to die, abnormally proliferate and initiate cancer stem cells. Metallocarboxypeptidases (MCPs) involved in multiple biological functions including inflammation, fibrosis and stem cell niche formation. This study aimed to evaluate the expression of carboxypeptidase 4 (CPA4) in hepatitis, liver cirrhosis and liver cancer tissues, and revealed its clinical significance in liver cancer progression. We firstly found that the CPA4 levels in tissues were significantly higher in liver cancer patients than those in other three groups. Then, elevated levels of CPA4 was observed in 57/100 (57%) liver cancer samples, and significantly correlated with Grade and Stage. We also identified a significant positive correlation between aberrant elevation of CPA4 and overexpression of stem cell markers including CD90, AFP and CD34 with follow-up data (n=100). Further Kaplan-Meier analysis confirmed that high levels of CPA4 and CD90 were significant predictors of poor overall survival. Multivariate Cox regression model showed that CPA4 was an independent prognostic factor for patients with liver cancer. This study demonstrated for the first time that high CPA4 expression was closely correlated with hepatocarcinogenesis, and might be used as an independent poor prognostic factor in liver cancer. Ivyspring International Publisher 2017-01-01 /pmc/articles/PMC5264046/ /pubmed/28123604 http://dx.doi.org/10.7150/jca.17060 Text en © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Sun, Lichao
Guo, Chunguang
Burnett, Joseph
Pan, Jian
Yang, Zhihua
Ran, Yuliang
Sun, Duxin
Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title_full Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title_fullStr Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title_full_unstemmed Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title_short Association between expression of Carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
title_sort association between expression of carboxypeptidase 4 and stem cell markers and their clinical significance in liver cancer development
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264046/
https://www.ncbi.nlm.nih.gov/pubmed/28123604
http://dx.doi.org/10.7150/jca.17060
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