Abstract
To identify novel biomarkers of metastasis of colorectal cancer (CRC), we developed an orthotopic implantation model of murine CRC and selected in vivo M5, a subclone of the SW480 CRC cell line with enhanced potential for metastasis to the liver. We compared the differences in the gene expression profiles between M5 and SW480 cells using gene expression profiling. We found that expression of special AT-rich sequence-binding protein 2 (SATB2) was down-regulated in M5 cells. Immunohistochemical analysis of 146 colorectal tumour samples showed that underexpression of SATB2 was strongly correlated with poor prognosis, tumour invasion, lymph node metastasis, distant metastasis, and Dukes' classification for CRC. Univariate and multivariate survival analyses further showed that SATB2 expression was a potential favourable prognostic factor for CRC. These results demonstrated not only that SATB2 is a potential novel prognostic factor for CRC, but also that selection of a highly metastatic clone of SW480 in vivo coupled with gene expression profiling is a powerful approach to identifying prognostic markers for CRC.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism*
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Animals
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Biomarkers, Tumor / genetics
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Blotting, Western / methods
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Cell Line, Tumor
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / secondary*
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Down-Regulation
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Female
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Gene Expression
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Gene Expression Profiling
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Humans
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Immunohistochemistry
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Liver Neoplasms / secondary*
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Lymphatic Metastasis
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Male
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Matrix Attachment Region Binding Proteins / analysis
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Matrix Attachment Region Binding Proteins / genetics*
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Matrix Attachment Region Binding Proteins / metabolism
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Mice
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Mice, Nude
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Middle Aged
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Models, Animal
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Neoplasm Staging
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Neoplasm Transplantation
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Oligonucleotide Array Sequence Analysis
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Prognosis
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Proportional Hazards Models
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RNA, Small Interfering / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Survival Analysis
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Transcription Factors / analysis
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transfection / methods
Substances
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Biomarkers, Tumor
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Matrix Attachment Region Binding Proteins
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RNA, Small Interfering
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SATB2 protein, human
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Transcription Factors