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

TitleGene expression profiling of liver cancer stem cells by RNA-sequencing
Authors
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
Citation
Plos One, 2012, v. 7 n. 5 How to Cite?
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. © 2012 Ho et al.
Persistent Identifierhttp://hdl.handle.net/10722/159925
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHo, DWYen_HK
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorYi, Ken_HK
dc.contributor.authorLam, CTen_HK
dc.contributor.authorNg, MNPen_HK
dc.contributor.authorYu, WCen_HK
dc.contributor.authorLau, Jen_HK
dc.contributor.authorWan, Ten_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorYan, Zen_HK
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2012-08-16T05:59:34Z-
dc.date.available2012-08-16T05:59:34Z-
dc.date.issued2012en_HK
dc.identifier.citationPlos One, 2012, v. 7 n. 5en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/159925-
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.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
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-sequencingen_HK
dc.typeArticleen_HK
dc.identifier.emailWang, X: xqwang@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityWang, X=rp00507en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0037159en_HK
dc.identifier.pmid22606345-
dc.identifier.pmcidPMC3351419-
dc.identifier.scopuseid_2-s2.0-84861010015en_HK
dc.identifier.hkuros202923en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84861010015&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue5en_HK
dc.identifier.isiWOS:000305339400071-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHo, DWY=55216337000en_HK
dc.identifier.scopusauthoridYang, ZF=39863860200en_HK
dc.identifier.scopusauthoridYi, K=54997690700en_HK
dc.identifier.scopusauthoridLam, CT=7402989860en_HK
dc.identifier.scopusauthoridNg, MNP=23478329500en_HK
dc.identifier.scopusauthoridYu, WC=55216510100en_HK
dc.identifier.scopusauthoridLau, J=55216456300en_HK
dc.identifier.scopusauthoridWan, T=55216621000en_HK
dc.identifier.scopusauthoridWang, X=17343159900en_HK
dc.identifier.scopusauthoridYan, Z=12793898300en_HK
dc.identifier.scopusauthoridLiu, H=55216431300en_HK
dc.identifier.scopusauthoridZhang, Y=54911516400en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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