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dc.contributor.authorAvci, M. E.en_US
dc.contributor.authorKonu, O.en_US
dc.contributor.authorYagci, T.en_US
dc.date.accessioned2016-02-08T10:06:02Z
dc.date.available2016-02-08T10:06:02Z
dc.date.issued2008en_US
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/11693/22885
dc.description.abstractBackground: SLIT-ROBO families of proteins mediate axon pathfinding and their expression is not solely confined to nervous system. Aberrant expression of SLIT-ROBO genes was repeatedly shown in a wide variety of cancers, yet data about their collective behavior in hepatocellular carcinoma (HCC) is missing. Hence, we quantified SLIT-ROBO transcripts in HCC cell lines, and in normal and tumor tissues from liver. Methods: Expression of SLIT-ROBO family members was quantified by real-time qRT-PCR in 14 HCC cell lines, 8 normal and 35 tumor tissues from the liver. ANOVA and Pearson's correlation analyses were performed in R environment, and different clinicopathological subgroups were pairwise compared in Minitab. Gene expression matrices of cell lines and tissues were analyzed by Mantel's association test. Results: Genewise hierarchical clustering revealed two subgroups with coordinate expression pattern in both the HCC cell lines and tissues: ROBO1, ROBO2, SLIT1 in one cluster, and ROBO4, SLIT2, SLIT3 in the other, respectively. Moreover, SLIT-ROBO expression predicted AFP-dependent subgrouping of HCC cell lines, but not that of liver tissues. ROBO1 and ROBO2 were significantly up-regulated, whereas SLIT3 was significantly down-regulated in cell lines with high-AFP background. When compared to normal liver tissue, ROBO1 was found to be significantly overexpressed, while ROBO4 was down-regulated in HCC. We also observed that ROBO1 and SLIT2 differentiated histopathological subgroups of liver tissues depending on both tumor staging and differentiation status. However, ROBO4 could discriminate poorly differentiated HCC from other subgroups. Conclusion: The present study is the first in comprehensive and quantitative evaluation of SLIT-ROBO family gene expression in HCC, and suggests that the expression of SLIT-ROBO genes is regulated in hepatocarcinogenesis. Our results implicate that SLIT-ROBO transcription profile is bi-modular in nature, and that each module shows intrinsic variability. We also provide quantitative evidence for potential use of ROBO1, ROBO4 and SLIT2 for prediction of tumor stage and differentiation status.en_US
dc.language.isoEnglishen_US
dc.source.titleBMC Canceren_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/1471-2407-8-392en_US
dc.subjectAlpha fetoproteinen_US
dc.subjectRoundabout receptoren_US
dc.subjectRoundabout receptor 1en_US
dc.subjectRoundabout receptor 2en_US
dc.subjectRoundabout receptor 4en_US
dc.subjectSlit proteinen_US
dc.subjectSlit1 proteinen_US
dc.subjectSlit2 proteinen_US
dc.subjectSlit3 proteinen_US
dc.subjectUnclassified drugen_US
dc.subjectAlpha fetoproteinen_US
dc.subjectCell surface receptoren_US
dc.subjectImmunoglobulin receptoren_US
dc.subjectMembrane proteinen_US
dc.subjectNerve proteinen_US
dc.subjectROBO4 protein, humanen_US
dc.subjectRoundabout receptoren_US
dc.subjectSignal peptideen_US
dc.subjectSlit homolog 2 proteinen_US
dc.subjectSLIT1 protein, humanen_US
dc.subjectSLIT3 protein, humanen_US
dc.subjectArticleen_US
dc.subjectCancer cell cultureen_US
dc.subjectCancer stagingen_US
dc.subjectCell differentiationen_US
dc.subjectControlled studyen_US
dc.subjectDown regulationen_US
dc.subjectGene expressionen_US
dc.subjectGene overexpressionen_US
dc.subjectHistopathologyen_US
dc.subjectHumanen_US
dc.subjectHuman cellen_US
dc.subjectHuman tissueen_US
dc.subjectLiver carcinogenesisen_US
dc.subjectLiver cell carcinomaen_US
dc.subjectProtein expressionen_US
dc.subjectReal time polymerase chain reactionen_US
dc.subjectUpregulationen_US
dc.subjectAnalysis of varianceen_US
dc.subjectCluster analysisen_US
dc.subjectGene expression profilingen_US
dc.subjectGene expression regulationen_US
dc.subjectGeneticsen_US
dc.subjectLiveren_US
dc.subjectMetabolismen_US
dc.subjectPathologyen_US
dc.subjectPhysiologyen_US
dc.subjectReverse transcription polymerase chain reactionen_US
dc.subjectTissue microarrayen_US
dc.subjectTumor cell lineen_US
dc.subjectAlpha-Fetoproteinsen_US
dc.subjectAnalysis of Varianceen_US
dc.subjectCarcinoma, Hepatocellularen_US
dc.subjectCell Line, Tumoren_US
dc.subjectCluster Analysisen_US
dc.subjectGene Expression Profilingen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectHumansen_US
dc.subjectIntercellular Signaling Peptides and Proteinsen_US
dc.subjectLiveren_US
dc.subjectMembrane Proteinsen_US
dc.subjectNerve Tissue Proteinsen_US
dc.subjectReceptors, Cell Surfaceen_US
dc.subjectReceptors, Immunologicen_US
dc.subjectReverse Transcriptase Polymerase Chain Reactionen_US
dc.subjectTissue Array Analysisen_US
dc.titleQuantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expressionen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage1en_US
dc.citation.epage11en_US
dc.citation.volumeNumber8en_US
dc.identifier.doi10.1186/1471-2407-8-392en_US
dc.publisherBioMed Centralen_US


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