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      Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression

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      Author(s)
      Avci, M. E.
      Konu, O.
      Yagci, T.
      Date
      2008
      Source Title
      BMC Cancer
      Print ISSN
      1471-2407
      Publisher
      BioMed Central
      Volume
      8
      Pages
      1 - 11
      Language
      English
      Type
      Article
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      Abstract
      Background: 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.
      Keywords
      Alpha fetoprotein
      Roundabout receptor
      Roundabout receptor 1
      Roundabout receptor 2
      Roundabout receptor 4
      Slit protein
      Slit1 protein
      Slit2 protein
      Slit3 protein
      Unclassified drug
      Alpha fetoprotein
      Cell surface receptor
      Immunoglobulin receptor
      Membrane protein
      Nerve protein
      ROBO4 protein, human
      Roundabout receptor
      Signal peptide
      Slit homolog 2 protein
      SLIT1 protein, human
      SLIT3 protein, human
      Article
      Cancer cell culture
      Cancer staging
      Cell differentiation
      Controlled study
      Down regulation
      Gene expression
      Gene overexpression
      Histopathology
      Human
      Human cell
      Human tissue
      Liver carcinogenesis
      Liver cell carcinoma
      Protein expression
      Real time polymerase chain reaction
      Upregulation
      Analysis of variance
      Cluster analysis
      Gene expression profiling
      Gene expression regulation
      Genetics
      Liver
      Metabolism
      Pathology
      Physiology
      Reverse transcription polymerase chain reaction
      Tissue microarray
      Tumor cell line
      Alpha-Fetoproteins
      Analysis of Variance
      Carcinoma, Hepatocellular
      Cell Line, Tumor
      Cluster Analysis
      Gene Expression Profiling
      Gene Expression Regulation, Neoplastic
      Humans
      Intercellular Signaling Peptides and Proteins
      Liver
      Membrane Proteins
      Nerve Tissue Proteins
      Receptors, Cell Surface
      Receptors, Immunologic
      Reverse Transcriptase Polymerase Chain Reaction
      Tissue Array Analysis
      Permalink
      http://hdl.handle.net/11693/22885
      Published Version (Please cite this version)
      http://dx.doi.org/10.1186/1471-2407-8-392
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