Document Detail


Gene expression profiling of colorectal mucinous adenocarcinomas.
MedLine Citation:
PMID:  20485009     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Although mucinous adenocarcinomas represent 6% to 19% of all colorectal adenocarcinomas, little is known about the genome-wide alterations associated with this malignancy. We have sought to characterize both the gene expression profiles of mucinous adenocarcinomas and their clinicopathologic features. METHODS: Tumors from 171 patients with primary colorectal cancer were profiled using the Affymetrix HG-U133Plus 2.0 GeneChip with characterization of clinicopathologic data. Gene ontology software was used to identify altered biologic pathways. RESULTS: Twenty (11.7%) mucinous adenocarcinomas and 151 (89.3%) nonmucinous adenocarcinomas were identified. Mucinous adenocarcinomas were more likely to be diagnosed with lymph node (LN) metastases (75% vs 51%, P = .04) and at a more advanced stage (85% vs 54%, P = .006) but long-term survival (5-y survival 58.9% vs 58.7%, P = NS) was similar. Mucinous adenocarcinomas displayed 182 upregulated and 135 downregulated genes. The most upregulated genes included those involved in cellular differentiation and mucin metabolism (eg, AQP3 + 4.6, MUC5AC +4.2, MUC2 + 2.8). Altered biologic pathways included those associated with mucin substrate metabolism (P = .002 and .02), amino acid metabolism (P = .02), and the mitogen-activated protein kinase cascade (P = .02). DISCUSSION: Using gene expression profiling of mucinous adenocarcinomas, we have identified the differential upregulation of genes involved in differentiation and mucin metabolism, as well as specific biologic pathways. These findings suggest that mucinous adenocarcinomas represent a genetically distinct variant of colorectal adencarcinoma and have implications for the development of targeted therapies.
Authors:
Marcovalerio Melis; Jonathan Hernandez; Erin M Siegel; James M McLoughlin; Quan P Ly; Rajesh M Nair; James M Lewis; Eric H Jensen; Michael D Alvarado; Domenico Coppola; Steve Eschrich; Gregory C Bloom; Timothy J Yeatman; David Shibata
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Diseases of the colon and rectum     Volume:  53     ISSN:  1530-0358     ISO Abbreviation:  Dis. Colon Rectum     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372764     Medline TA:  Dis Colon Rectum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  936-43     Citation Subset:  IM    
Affiliation:
Department of Surgery, New York University Medical School and NYHHS VA, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics*,  pathology
Adenocarcinoma, Mucinous / genetics*,  pathology
Analysis of Variance
Aquaporin 3 / genetics
Chi-Square Distribution
Colorectal Neoplasms / genetics*,  pathology
Gene Expression Profiling*
Humans
Lymphatic Metastasis
Microarray Analysis
Mucin 5AC / genetics
Mucin-2 / genetics
Proportional Hazards Models
Survival Rate
Chemical
Reg. No./Substance:
0/AQP3 protein, human; 0/MUC2 protein, human; 0/MUC5AC protein, human; 0/Mucin 5AC; 0/Mucin-2; 158801-98-0/Aquaporin 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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