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Expression of selenium-binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer.
- Source :
-
Molecular nutrition & food research [Mol Nutr Food Res] 2008 Nov; Vol. 52 (11), pp. 1289-99. - Publication Year :
- 2008
-
Abstract
- To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
- Subjects :
- Adult
Aged
Aged, 80 and over
Cell Line, Tumor
Colonic Neoplasms genetics
Colorectal Neoplasms pathology
Humans
Intestinal Mucosa pathology
Intestinal Mucosa physiopathology
Intestines pathology
Middle Aged
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Prognosis
RNA, Small Interfering genetics
Rectal Neoplasms genetics
Selenium-Binding Proteins metabolism
Survivors
Colorectal Neoplasms genetics
Intestines physiopathology
Selenium-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1613-4133
- Volume :
- 52
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Molecular nutrition & food research
- Publication Type :
- Academic Journal
- Accession number :
- 18435490
- Full Text :
- https://doi.org/10.1002/mnfr.200700331