Gene expression profiling of liver cancer stem cells by RNA-sequencing.

<h4>Background</h4>Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90(+) liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these...

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Autores principales:	David W Y Ho, Zhen Fan Yang, Kang Yi, Chi Tat Lam, Michael N P Ng, Wan Ching Yu, Joyce Lau, Timothy Wan, Xiaoqi Wang, Zhixiang Yan, Hang Liu, Yong Zhang, Sheung Tat Fan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd2441a51a0a462887d35f9454e72a57
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spelling	oai:doaj.org-article:cd2441a51a0a462887d35f9454e72a572021-11-18T07:18:59ZGene expression profiling of liver cancer stem cells by RNA-sequencing.1932-620310.1371/journal.pone.0037159https://doaj.org/article/cd2441a51a0a462887d35f9454e72a572012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22606345/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90(+) liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90(+) cells sorted from tumor (CD90(+)CSCs) with parallel non-tumorous liver tissues (CD90(+)NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis.<h4>Methodology/principal findings</h4>CD90(+) cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90(+) cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90(+)CSCs and CD90(+)NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90(+)CSCs and CD90(+)NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90(+)CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90(+)CSCs compared to CD90(+)NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90(+)CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90(+)CSCs in liver tumor tissues.<h4>Conclusions/significance</h4>The identified genes, such as GPC3 that are distinctly expressed in liver CD90(+)CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells.David W Y HoZhen Fan YangKang YiChi Tat LamMichael N P NgWan Ching YuJoyce LauTimothy WanXiaoqi WangZhixiang YanHang LiuYong ZhangSheung Tat FanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37159 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David W Y Ho Zhen Fan Yang Kang Yi Chi Tat Lam Michael N P Ng Wan Ching Yu Joyce Lau Timothy Wan Xiaoqi Wang Zhixiang Yan Hang Liu Yong Zhang Sheung Tat Fan Gene expression profiling of liver cancer stem cells by RNA-sequencing.
description	<h4>Background</h4>Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90(+) liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90(+) cells sorted from tumor (CD90(+)CSCs) with parallel non-tumorous liver tissues (CD90(+)NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis.<h4>Methodology/principal findings</h4>CD90(+) cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90(+) cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90(+)CSCs and CD90(+)NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90(+)CSCs and CD90(+)NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90(+)CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90(+)CSCs compared to CD90(+)NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90(+)CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90(+)CSCs in liver tumor tissues.<h4>Conclusions/significance</h4>The identified genes, such as GPC3 that are distinctly expressed in liver CD90(+)CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells.
format	article
author	David W Y Ho Zhen Fan Yang Kang Yi Chi Tat Lam Michael N P Ng Wan Ching Yu Joyce Lau Timothy Wan Xiaoqi Wang Zhixiang Yan Hang Liu Yong Zhang Sheung Tat Fan
author_facet	David W Y Ho Zhen Fan Yang Kang Yi Chi Tat Lam Michael N P Ng Wan Ching Yu Joyce Lau Timothy Wan Xiaoqi Wang Zhixiang Yan Hang Liu Yong Zhang Sheung Tat Fan
author_sort	David W Y Ho
title	Gene expression profiling of liver cancer stem cells by RNA-sequencing.
title_short	Gene expression profiling of liver cancer stem cells by RNA-sequencing.
title_full	Gene expression profiling of liver cancer stem cells by RNA-sequencing.
title_fullStr	Gene expression profiling of liver cancer stem cells by RNA-sequencing.
title_full_unstemmed	Gene expression profiling of liver cancer stem cells by RNA-sequencing.
title_sort	gene expression profiling of liver cancer stem cells by rna-sequencing.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cd2441a51a0a462887d35f9454e72a57
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Gene expression profiling of liver cancer stem cells by RNA-sequencing.

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