Gene expression profiling of colorectal mucinous adenocarcinomas.
OBJECTIVE
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).


CONCLUSIONS
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.
Melis
Marcovalerio
M
Department of Surgery, New York University Medical School and NYHHS VA, New York, New York, USA.
Hernandez
Jonathan
J
Siegel
Erin M
EM
McLoughlin
James M
JM
Ly
Quan P
QP
Nair
Rajesh M
RM
Lewis
James M
JM
Jensen
Eric H
EH
Alvarado
Michael D
MD
Coppola
Domenico
D
Eschrich
Steve
S
Bloom
Gregory C
GC
Yeatman
Timothy J
TJ
Shibata
David
D
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000704:Analysis of Variance; D051400:Aquaporin 3 / Q000235:genetics; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D046228:Microarray Analysis; D055271:Mucin 5AC / Q000235:genetics; D055262:Mucin-2 / Q000235:genetics; D016016:Proportional Hazards Models; D015996:Survival Rate
C496027:AQP3 protein, human; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D051400:Aquaporin 3