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Right-side and left-side colon cancer follow different pathways to relapse.
- Source :
-
Molecular carcinogenesis [Mol Carcinog] 2012 May; Vol. 51 (5), pp. 411-21. Date of Electronic Publication: 2011 Jun 07. - Publication Year :
- 2012
-
Abstract
- There is growing evidence that cancer of the ascending (right-side) colon is different from cancer of the descending (left-side) colon at the molecular level. Using microarray data from 102 right-side colon carcinomas and 95 left-side colon carcinomas we show that different pathways dominate progression to relapse in right-side and left-side colon cancer. Right-side tumors at a high risk for relapse exhibit elevated expression of cell cycle control genes and elevated Wnt signaling. On the other hand, relapse-prone left-side tumors show elevated expression of genes that promote stromal expansion and reduced expression of tumor suppressor genes that initiate Wnt signaling. Single gene prognostic biomarkers are found separately for right-side and left-side disease. In left-side tumors with low expression levels of NADPH oxidase 4 (NOX4) the 5-yr relapse-free survival probability is 0.89 95% CI (0.80-0.99), and in tumors with elevated NOX4 expression the probability is 0.51 95% CI (0.37-0.70). Right-side tumors with elevated expression levels of caudal type homeobox 2 (CDX2) have a 5-yr relapse-free survival probability of 0.88 95% CI (0.80-0.96), and those with low CDX2 expression have a corresponding probability of 0.39 95% CI (0.15-0.78). Both NOX4 and CDX2 are much less prognostic on the opposite sides. This newly identified role of NOX4 in colon cancer is further investigated using the SW620 lymph node metastasis colon adenocarcinoma cell line and RNA interference. We show that NOX4 is expressed in the SW620 cell line and that application of NOX4 siRNA causes a significant reduction in reactive oxidative species production.<br /> (Copyright © 2011 Wiley Periodicals, Inc.)
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
CDX2 Transcription Factor
Cell Cycle Checkpoints genetics
Colonic Neoplasms genetics
Colonic Neoplasms pathology
Disease-Free Survival
Female
Homeodomain Proteins genetics
Humans
Male
NADPH Oxidase 4
NADPH Oxidases genetics
Neoplasm Staging
RNA, Small Interfering
Recurrence
Tumor Suppressor Proteins genetics
Wnt Signaling Pathway genetics
Adenocarcinoma metabolism
Colonic Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Homeodomain Proteins metabolism
NADPH Oxidases metabolism
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2744
- Volume :
- 51
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 21656576
- Full Text :
- https://doi.org/10.1002/mc.20804