Gene expression profiling of colorectal mucinous adenocarcinomas

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

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 HGU133Plus 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.

Original languageEnglish (US)
Pages (from-to)936-943
Number of pages8
JournalDiseases of the Colon and Rectum
Volume53
Issue number6
DOIs
Publication statusPublished - Jun 1 2010

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Keywords

  • Colorectal cancer
  • Microarray
  • Mucinous

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Melis, M., Hernandez, J., Siegel, E. M., McLoughlin, J. M., Ly, Q. P., Nair, R. M., ... Shibata, D. (2010). Gene expression profiling of colorectal mucinous adenocarcinomas. Diseases of the Colon and Rectum, 53(6), 936-943. https://doi.org/10.1007/DCR.0b013e3181d320c4