Gene expression profiling of colorectal mucinous adenocarcinomas

Marcovalerio Melis, Jonathan Hernandez, Erin M. Siegel, James Mcloughlin, Quan P. Ly, Rajesh M. Nair, James Lewis, Eric H. Jensen, Michael D. Alvarado, Domenico Coppola, Steve Eschrich, Gregory C. Bloom, Timothy J. Yeatman, David Shibata

Research output: Contribution to journalArticle

25 Citations (Scopus)

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
StatePublished - Jun 1 2010

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Mucinous Adenocarcinoma
Gene Expression Profiling
Mucins
Adenocarcinoma
Genes
Gene Ontology
Survival
Mitogen-Activated Protein Kinases
Transcriptome
Colorectal Neoplasms
Neoplasms
Up-Regulation
Down-Regulation
Software
Lymph Nodes
Genome
Neoplasm Metastasis
Amino Acids

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Gene expression profiling of colorectal mucinous adenocarcinomas. / Melis, Marcovalerio; Hernandez, Jonathan; Siegel, Erin M.; Mcloughlin, James; Ly, Quan P.; Nair, Rajesh M.; Lewis, James; Jensen, Eric H.; Alvarado, Michael D.; Coppola, Domenico; Eschrich, Steve; Bloom, Gregory C.; Yeatman, Timothy J.; Shibata, David.

In: Diseases of the Colon and Rectum, Vol. 53, No. 6, 01.06.2010, p. 936-943.

Research output: Contribution to journalArticle

Melis, M, Hernandez, J, Siegel, EM, Mcloughlin, J, Ly, QP, Nair, RM, Lewis, J, Jensen, EH, Alvarado, MD, Coppola, D, Eschrich, S, Bloom, GC, Yeatman, TJ & Shibata, D 2010, 'Gene expression profiling of colorectal mucinous adenocarcinomas', Diseases of the Colon and Rectum, vol. 53, no. 6, pp. 936-943. https://doi.org/10.1007/DCR.0b013e3181d320c4
Melis, Marcovalerio ; Hernandez, Jonathan ; Siegel, Erin M. ; Mcloughlin, James ; Ly, Quan P. ; Nair, Rajesh M. ; Lewis, James ; Jensen, Eric H. ; Alvarado, Michael D. ; Coppola, Domenico ; Eschrich, Steve ; Bloom, Gregory C. ; Yeatman, Timothy J. ; Shibata, David. / Gene expression profiling of colorectal mucinous adenocarcinomas. In: Diseases of the Colon and Rectum. 2010 ; Vol. 53, No. 6. pp. 936-943.
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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.",
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T1 - Gene expression profiling of colorectal mucinous adenocarcinomas

AU - Melis, Marcovalerio

AU - Hernandez, Jonathan

AU - Siegel, Erin M.

AU - Mcloughlin, James

AU - Ly, Quan P.

AU - Nair, Rajesh M.

AU - Lewis, James

AU - Jensen, Eric H.

AU - Alvarado, Michael D.

AU - Coppola, Domenico

AU - Eschrich, Steve

AU - Bloom, Gregory C.

AU - Yeatman, Timothy J.

AU - Shibata, David

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N2 - 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.

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