File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Gene expression profiling of liver cancer stem cells by RNA-sequencing
  • Basic View
  • Metadata View
  • XML View
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 2
Yan, Z3
Liu, H3
Zhang, Y3
Fan, ST2 2
 
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
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
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
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
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
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Ho, DWY</contributor.author>
<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>
<contributor.author>Liu, H</contributor.author>
<contributor.author>Zhang, Y</contributor.author>
<contributor.author>Fan, ST</contributor.author>
<date.accessioned>2012-08-16T05:59:34Z</date.accessioned>
<date.available>2012-08-16T05:59:34Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>Plos One, 2012, v. 7 n. 5</identifier.citation>
<identifier.issn>1932-6203</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/159925</identifier.uri>
<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>
<language>eng</language>
<publisher>Public Library of Science. The Journal&apos;s web site is located at http://www.plosone.org/home.action</publisher>
<relation.ispartof>PLoS ONE</relation.ispartof>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<subject>Cancer patient</subject>
<subject>Cancer stem cell</subject>
<subject>Cell selection</subject>
<subject>Flow cytometry</subject>
<subject>Gene amplification</subject>
<title>Gene expression profiling of liver cancer stem cells by RNA-sequencing</title>
<type>Article</type>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1371/journal.pone.0037159</identifier.doi>
<identifier.pmid>22606345</identifier.pmid>
<identifier.pmcid>PMC3351419</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-84861010015</identifier.scopus>
<identifier.hkuros>202923</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-84861010015&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>7</identifier.volume>
<identifier.issue>5</identifier.issue>
<publisher.place>United States</publisher.place>
<bitstream.url>http://hub.hku.hk/bitstream/10722/159925/1/content.pdf</bitstream.url>
</item>
Author Affiliations
  1. AstraZeneca
  2. The University of Hong Kong
  3. Beijing Genomics Institute, Shenzhen