Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression
Date
2008Source Title
BMC Cancer
Print ISSN
1471-2407
Publisher
BioMed Central
Volume
8
Pages
1 - 11
Language
English
Type
ArticleItem Usage Stats
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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 fetoproteinRoundabout 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/11693/22885Published Version (Please cite this version)
http://dx.doi.org/10.1186/1471-2407-8-392Collections
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