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Open Access Highly Accessed Research article

EMT is the dominant program in human colon cancer

Andre Loboda1, Michael V Nebozhyn1, James W Watters1, Carolyne A Buser3, Peter Martin Shaw2, Pearl S Huang3, Laura Van't Veer7, Rob AEM Tollenaar8, David B Jackson6, Deepak Agrawal5, Hongyue Dai4 and Timothy J Yeatman5*

Author Affiliations

1 Merck, Sharp and Dohme, P.O. Box 4, 770 Sumneytown Pike, Building 53, West Point, PA 19486, USA

2 Merck, Sharp and Dohme, P.O. Box 4, 770 Sumneytown Pike, WP53B-120, West Point, PA 19486, USA

3 Merck Research Laboratories, UG-4C74, 351 N. Sumneytown Pike, North Wales, PA 19454-2505, USA

4 Merck, Sharp and Dohme, 33 Avenue Louis Pasteur, Boston, MA 02115, USA

5 Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA

6 LIFE Biosystems GmbH, Poststrasse 34, D-69115 Heidelberg, Germany

7 Diagnostic Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

8 Leiden University Medical Center, PO Box 9600 2300 RC Leiden, The Netherlands

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BMC Medical Genomics 2011, 4:9  doi:10.1186/1755-8794-4-9

Published: 20 January 2011

Abstract

Background

Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging.

Methods

We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1) of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence.

Results

Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1) was tightly correlated (Pearson R = 0.92, P < 10-135) with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT.

Conclusions

These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.