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Article: Gene expression profiling of liver cancer stem cells by RNA-sequencing
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TitleGene expression profiling of liver cancer stem cells by RNA-sequencing
 
AuthorsHo, DWY2
Yang, ZF2 1
Yi, K3
Lam, CT2
Ng, MNP2
Yu, WC2
Lau, J2
Wan, T2
Wang, X2
Yan, Z3
Liu, H3
Zhang, Y3
Fan, ST2
 
KeywordsCancer patient
Cancer stem cell
Cell selection
Flow cytometry
Gene amplification
 
Issue Date2012
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2012, v. 7 n. 5 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0037159
 
AbstractBackground: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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. © 2012 Ho et al.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0037159
 
PubMed Central IDPMC3351419
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorHo, DWY
 
dc.contributor.authorYang, ZF
 
dc.contributor.authorYi, K
 
dc.contributor.authorLam, CT
 
dc.contributor.authorNg, MNP
 
dc.contributor.authorYu, WC
 
dc.contributor.authorLau, J
 
dc.contributor.authorWan, T
 
dc.contributor.authorWang, X
 
dc.contributor.authorYan, Z
 
dc.contributor.authorLiu, H
 
dc.contributor.authorZhang, Y
 
dc.contributor.authorFan, ST
 
dc.date.accessioned2012-08-16T05:59:34Z
 
dc.date.available2012-08-16T05:59:34Z
 
dc.date.issued2012
 
dc.description.abstractBackground: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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. © 2012 Ho et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2012, v. 7 n. 5 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0037159
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0037159
 
dc.identifier.hkuros202923
 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue5
 
dc.identifier.pmcidPMC3351419
 
dc.identifier.pmid22606345
 
dc.identifier.scopuseid_2-s2.0-84861010015
 
dc.identifier.urihttp://hdl.handle.net/10722/159925
 
dc.identifier.volume7
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subjectCancer patient
 
dc.subjectCancer stem cell
 
dc.subjectCell selection
 
dc.subjectFlow cytometry
 
dc.subjectGene amplification
 
dc.titleGene expression profiling of liver cancer stem cells by RNA-sequencing
 
dc.typeArticle
 
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<contributor.author>Yang, ZF</contributor.author>
<contributor.author>Yi, K</contributor.author>
<contributor.author>Lam, CT</contributor.author>
<contributor.author>Ng, MNP</contributor.author>
<contributor.author>Yu, WC</contributor.author>
<contributor.author>Lau, J</contributor.author>
<contributor.author>Wan, T</contributor.author>
<contributor.author>Wang, X</contributor.author>
<contributor.author>Yan, Z</contributor.author>
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<description.abstract>Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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. &#169; 2012 Ho et al.</description.abstract>
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<subject>Cancer patient</subject>
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Author Affiliations
  1. AstraZeneca
  2. The University of Hong Kong
  3. Beijing Genomics Institute, Shenzhen