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Article: Topological and functional discovery in a gene coexpression meta-network of gastric cancer

TitleTopological and functional discovery in a gene coexpression meta-network of gastric cancer
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2006, v. 66 n. 1, p. 232-241 How to Cite?
AbstractGastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we assembled and systematically analyzed a consensus gene coexpression meta-network of gastric cancer incorporating >300 tissue samples from four independent patient populations (the "gastrome"). We find that the gastrome exhibits a hierarchical scale-free architecture, with an internal structure comprising multiple deeply embedded modules associated with diverse cellular functions. Individual modules display distinct subtopologies, with some (cellular proliferation) being integrated within the primary network, and others (ribosomal biosynthesis) being relatively isolated. One module associated with intestinal differentiation exhibited a remarkably high degree of autonomy, raising the possibility that its specific topological features may contribute towards the frequent occurrence of intestinal metaplasia in gastric cancer. At the single-gene level, we discovered a novel conserved interaction between the PLA2G2A prognostic marker and the EphB2 receptor, and used tissue microarrays to validate the PLA2G2A/EphB2 association. Finally, because EphB2 is a known target of the Wnt signaling pathway, we tested and provide evidence that the Wnt pathway may also similarly regulate PLA2G2A. Many of these findings were not discernible by studying the single patient populations in isolation. Thus, besides enhancing our knowledge of gastric cancer, our results show the broad utility of applying meta-analytic approaches to genome-wide data for the purposes of biological discovery. ©2006 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/88352
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAggarwal, Aen_HK
dc.contributor.authorGuo, DLen_HK
dc.contributor.authorHoshida, Yen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorSo, Sen_HK
dc.contributor.authorBoussioutas, Aen_HK
dc.contributor.authorChen, Xen_HK
dc.contributor.authorBowtell, Den_HK
dc.contributor.authorAburatani, Hen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorTan, Pen_HK
dc.date.accessioned2010-09-06T09:42:15Z-
dc.date.available2010-09-06T09:42:15Z-
dc.date.issued2006en_HK
dc.identifier.citationCancer Research, 2006, v. 66 n. 1, p. 232-241en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88352-
dc.description.abstractGastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we assembled and systematically analyzed a consensus gene coexpression meta-network of gastric cancer incorporating >300 tissue samples from four independent patient populations (the "gastrome"). We find that the gastrome exhibits a hierarchical scale-free architecture, with an internal structure comprising multiple deeply embedded modules associated with diverse cellular functions. Individual modules display distinct subtopologies, with some (cellular proliferation) being integrated within the primary network, and others (ribosomal biosynthesis) being relatively isolated. One module associated with intestinal differentiation exhibited a remarkably high degree of autonomy, raising the possibility that its specific topological features may contribute towards the frequent occurrence of intestinal metaplasia in gastric cancer. At the single-gene level, we discovered a novel conserved interaction between the PLA2G2A prognostic marker and the EphB2 receptor, and used tissue microarrays to validate the PLA2G2A/EphB2 association. Finally, because EphB2 is a known target of the Wnt signaling pathway, we tested and provide evidence that the Wnt pathway may also similarly regulate PLA2G2A. Many of these findings were not discernible by studying the single patient populations in isolation. Thus, besides enhancing our knowledge of gastric cancer, our results show the broad utility of applying meta-analytic approaches to genome-wide data for the purposes of biological discovery. ©2006 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshCluster Analysisen_HK
dc.subject.meshGene Expression Profilingen_HK
dc.subject.meshGroup II Phospholipases A2en_HK
dc.subject.meshHumansen_HK
dc.subject.meshOligonucleotide Array Sequence Analysisen_HK
dc.subject.meshPhospholipases A - biosynthesis - geneticsen_HK
dc.subject.meshReceptor, EphB2 - biosynthesis - geneticsen_HK
dc.subject.meshStomach Neoplasms - genetics - metabolism - pathologyen_HK
dc.titleTopological and functional discovery in a gene coexpression meta-network of gastric canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=66&issue=1&spage=232&epage=41&date=2006&atitle=Topological+and+functional+discovery+in+a+gene+coexpression+meta-network+of+gastric+canceren_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-05-2232en_HK
dc.identifier.pmid16397236-
dc.identifier.scopuseid_2-s2.0-31544460919en_HK
dc.identifier.hkuros113972en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-31544460919&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume66en_HK
dc.identifier.issue1en_HK
dc.identifier.spage232en_HK
dc.identifier.epage241en_HK
dc.identifier.isiWOS:000234529500030-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10009152-
dc.identifier.scopusauthoridAggarwal, A=7201563922en_HK
dc.identifier.scopusauthoridGuo, DL=7403332449en_HK
dc.identifier.scopusauthoridHoshida, Y=24597037700en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridSo, S=7102397384en_HK
dc.identifier.scopusauthoridBoussioutas, A=8745611400en_HK
dc.identifier.scopusauthoridChen, X=8978110800en_HK
dc.identifier.scopusauthoridBowtell, D=35271003200en_HK
dc.identifier.scopusauthoridAburatani, H=7005377301en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridTan, P=7201942033en_HK
dc.identifier.citeulike997168-

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