EMT is the Dominant Program in Human Colon Cancer

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2011 Jan 22

PMID 21251323

Citations 174

Authors

Andre Loboda

Michael V Nebozhyn

James W Watters

Carolyne A Buser

Peter Martin Shaw

Pearl S Huang

Laura Vant Veer

Rob A E M Tollenaar

David B Jackson

Deepak Agrawal

Hongyue Dai

Timothy J Yeatman

Affiliations

Soon will be listed here.

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.

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References

Eschrich S, Yang I, Bloom G, Kwong K, Boulware D, Cantor A . Molecular staging for survival prediction of colorectal cancer patients. J Clin Oncol. 2005; 23(15):3526-35. DOI: 10.1200/JCO.2005.00.695. View

Dyrskjot L, Zieger K, Real F, Malats N, Carrato A, Hurst C . Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res. 2007; 13(12):3545-51. DOI: 10.1158/1078-0432.CCR-06-2940. View

Bertucci F, Finetti P, Cervera N, Charafe-Jauffret E, Mamessier E, Adelaide J . Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res. 2006; 66(9):4636-44. DOI: 10.1158/0008-5472.CAN-06-0031. View

Agrawal D, Chen T, Irby R, Quackenbush J, Chambers A, Szabo M . Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst. 2002; 94(7):513-21. DOI: 10.1093/jnci/94.7.513. View

Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B . Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007; 13(11):3207-14. DOI: 10.1158/1078-0432.CCR-06-2765. View

Park S, Gaur A, Lengyel E, Peter M . The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008; 22(7):894-907. PMC: 2279201. DOI: 10.1101/gad.1640608. View

Rosser C, Liu L, Sun Y, Villicana P, McCullers M, Porvasnik S . Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia. Cancer Epidemiol Biomarkers Prev. 2009; 18(2):444-53. PMC: 2729268. DOI: 10.1158/1055-9965.EPI-08-1002. View

Jorissen R, Gibbs P, Christie M, Prakash S, Lipton L, Desai J . Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer. Clin Cancer Res. 2009; 15(24):7642-7651. PMC: 2920750. DOI: 10.1158/1078-0432.CCR-09-1431. View

Huang E, Ishida S, Pittman J, Dressman H, Bild A, Kloos M . Gene expression phenotypic models that predict the activity of oncogenic pathways. Nat Genet. 2003; 34(2):226-30. DOI: 10.1038/ng1167. View

10.

Malvezzi M, Bertuccio P, Chatenoud L, Negri E, La Vecchia C, Decarli A . Cancer mortality in Italy, 2003. Tumori. 2010; 95(6):655-64. DOI: 10.1177/030089160909500603. View

11.

Pino M, Kikuchi H, Zeng M, Herraiz M, Sperduti I, Berger D . Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology. 2009; 138(4):1406-17. PMC: 2846966. DOI: 10.1053/j.gastro.2009.12.010. View

12.

Wang Y, Jatkoe T, Zhang Y, Mutch M, Talantov D, Jiang J . Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer. J Clin Oncol. 2004; 22(9):1564-71. DOI: 10.1200/JCO.2004.08.186. View

13.

Smith J, Deane N, Wu F, Merchant N, Zhang B, Jiang A . Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology. 2009; 138(3):958-68. PMC: 3388775. DOI: 10.1053/j.gastro.2009.11.005. View

14.

Lin Y, Friederichs J, Black M, Mages J, Rosenberg R, Guilford P . Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin Cancer Res. 2007; 13(2 Pt 1):498-507. DOI: 10.1158/1078-0432.CCR-05-2734. View

15.

Enriquez J, Diez M, Tobaruela E, Lozano O, Dominguez P, Gonzalez A . Clinical, histopathological, cytogenetic and prognostic differences between mucinous and nonmucinous colorectal adenocarcinomas. Rev Esp Enferm Dig. 1998; 90(8):563-72. View

16.

Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N . A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009; 15(6):489-500. PMC: 2743093. DOI: 10.1016/j.ccr.2009.03.022. View

17.

Dressman H, Hans C, Bild A, Olson J, Rosen E, Marcom P . Gene expression profiles of multiple breast cancer phenotypes and response to neoadjuvant chemotherapy. Clin Cancer Res. 2006; 12(3 Pt 1):819-26. DOI: 10.1158/1078-0432.CCR-05-1447. View

18.

Kruhoffer M, Jensen J, Laiho P, Dyrskjot L, Salovaara R, Arango D . Gene expression signatures for colorectal cancer microsatellite status and HNPCC. Br J Cancer. 2005; 92(12):2240-8. PMC: 2361815. DOI: 10.1038/sj.bjc.6602621. View

19.

Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G . Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008; 14(16):5158-65. DOI: 10.1158/1078-0432.CCR-07-4756. View

20.

Bild A, Yao G, Chang J, Wang Q, Potti A, Chasse D . Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2005; 439(7074):353-7. DOI: 10.1038/nature04296. View