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Journal of Cancer Research and Clinical Oncology

Published in:

01-05-2003 | Original Paper

Classification of Dukes' B and C colorectal cancers using expression arrays

Authors: Casper Møller Frederiksen, Steen Knudsen, Søren Laurberg, Torben F. Ørntoft

Published in: Journal of Cancer Research and Clinical Oncology | Issue 5/2003

Abstract

Purpose

Colorectal cancer is one of the most common malignancies. Substaging of the cancer is of importance not only to prognosis but also to treatment. Classification of substages based on DNA microarray technology is currently the most promising approach. We therefore investigated if gene expression microarrays could be used to classify colorectal tumors.

Methods

We used the Affymetrix oligonucleotide arrays to analyze the expression of more than 5,000 genes in samples from the sigmoid and upper rectum of the left colon. Five samples were from normal mucosa and five samples from each of the Dukes' stages A, B, C, and D. Expression data were filtered based on either covariance or a selection of the most significantly varying genes between tumor stages.

Results

A nearest neighbor classifier was used to classify normal, and Dukes' B and C samples with less than 20% error, whereas Dukes' A and D could not be classified correctly. A number of interesting gene clusters showed a discriminating difference between Dukes' B and C samples. These included mitochondrial genes, stromal remodeling genes, and genes related to cell adhesion.

Conclusion

Molecular classification based on gene expression of one of the most common malignancies, colorectal cancer, now seems to be within reach. The data indicates that it is possible at least to classify Dukes' B and C colorectal tumors with microarrays.

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson JJ, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511PubMed

Alizadeh AA, Ross DT, Perou CM, van de RM, (2001) Towards a novel classification of human malignancies based on gene expression patterns. J Pathol 195:41–52CrossRefPubMed

Alon U, Barkai N, Notterman DA, Gish K, Ybarra S, Mack D, Levine AJ (1999) Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA 96:6745–6750PubMed

Ariel I, de Groot N, Hochberg A (2000) Imprinted H19 gene expression in embryogenesis and human cancer: the oncofetal connection. Am J Med Genet 91:46–50CrossRefPubMed

Battegay EJ (1995) Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med 73:333–346PubMed

Birkenkamp-Demtroder K, Christensen LL, Olesen SH, Frederiksen CM, Laiho P, Aaltonen LA, Laurberg S, Sorensen FB, Hagemann R, Orntoft TF (2002) Gene expression in colorectal cancer. Cancer Res 62:4352–4363PubMed

de Fraipont F, Nicholson AC, Feige JJ, Van Meir EG (2001) Thrombospondins and tumor angiogenesis. Trends Mol Med 7:401–407CrossRefPubMed

del Re EC, Shuja S, Cai J, Murnane MJ (2000) Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas. Br J Cancer 82:1317–1326CrossRefPubMed

Demange P, Voges D, Benz J, Liemann S, Gottig P, Berendes R, Burger A, Huber R (1994) Annexin V: the key to understanding ion selectivity and voltage regulation? Trends Biochem Sci 19:272–276

DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM (1996) Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 14:457–460

Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta KJ, Rubin MA, Chinnaiyan AM (2001) Delineation of prognostic biomarkers in prostate cancer. Nature 412:822–826

Dukes CE (1932) The classification of cancer in the rectum. J Pathol Bacteriol 35:323

Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863–14868PubMed

Furey TS, Cristianini N, Duffy N, Bednarski DW, Schummer M, Haussler D (2000) Support vector machine classification and validation of cancer tissue samples using microarray expression data. Bioinformatics 16:906–914CrossRefPubMed

Getz G, Levine E, Domany E (2000) Coupled two-way clustering analysis of gene microarray data. Proc Natl Acad Sci USA 97:12079–12084CrossRefPubMed

Itzkowitz SH (1992) Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms. J Cell Biochem Suppl 16G:97–101PubMed

Li C, Hung WW (2001) Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol 2: RESEARCH0032PubMed

Li C, Wong WH (2001) Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection. Proc Natl Acad Sci USA 2001 98:31–36CrossRef

Mandel JS, Church TR, Ederer F, Bond JH (1999) Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 91:434–437CrossRefPubMed

Mandel U, Langkilde NC, Orntoft TF, Therkildsen MH, Karkov J, Reibel J, White T, Clausen H, Dabelsteen E (1992) Expression of histo-blood-group-A/B-gene-defined glycosyltransferases in normal and malignant epithelia: correlation with A/B-carbohydrate expression. Int J Cancer 19:7–12

Newland RC, Chapuis PH, Smyth EJ (1987) The prognostic value of substaging colorectal carcinoma. A prospective study of 1117 cases with standardized pathology. Cancer 60:852–857PubMed

Notterman DA, Alon U, Sierk AJ, Levine AJ (2001) Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays. Cancer Res 61:3124–3130PubMed

Ohtani H (1998) Stromal reaction in cancer tissue: pathophysiologic significance of the expression of matrix-degrading enzymes in relation to matrix turnover and immune/inflammatory reactions. Pathol Int 48:1–9PubMed

Okuno K, Yasutomi M, Nishimura N, Arakawa T, Shiomi M, Hida J, Ueda K, Minami K (2001) Gene expression analysis in colorectal cancer using practical DNA array filter. Dis Colon Rectum 44:295–299PubMed

Orntoft TF, Mors NP, Eriksen G, Jacobsen NO, Poulsen HS (1985) Comparative immunoperoxidase demonstration of T-antigens in human colorectal carcinomas and morphologically abnormal mucosa. Cancer Res 45:447–452PubMed

Orntoft TF, Greenwell P, Clausen H, Watkins WM (1991) Regulation of the oncodevelopmental expression of type 1 chain ABH and Lewis(b) blood group antigens in human colon by alpha-2-L-fucosylation. Gut 32:287–293PubMed

Polette M, Birembaut P (1998) Membrane-type metalloproteinases in tumor invasion. Int J Biochem Cell Biol 30:1195–1202CrossRefPubMed

Ponz dL, Sacchetti C, Sassatelli R, Zanghieri G, Roncucci L, Scalmati A (1990) Evidence for the existence of different types of large bowel tumor: suggestions from the clinical data of a population-based registry. J Surg Oncol 44:35–43PubMed

Pyke C, Ralfkiaer E, Ronne E, Hoyer-Hansen G, Kirkeby L, Dano K (1994) Immunohistochemical detection of the receptor for urokinase plasminogen activator in human colon cancer. Histopathology 24:131–138PubMed

Sadler TW, Langman J (1990) Langman's Medical Embryology. Lippincott Wiliams & Wilkins, Portland, p 242

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de RM, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein LP, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMed

Thykjaer T, Workman C, Kruhoffer M, Demtroder K, Wolf H, Andersen LD, Frederiksen CM, Knudsen S, Orntoft TF (2001) Identification of gene expression patterns in superficial and invasive human bladder cancer. Cancer Res 61:2492–2499PubMed

Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116–5121PubMed

Underwood JC (1974) Lymphoreticular infiltration in human tumours: prognostic and biological implications: a review. Br J Cancer 30:538–548PubMed

Vlems FA, Diestra JH, Cornelissen IM, Ruers TJ, Ligtenberg MJ, Punt CJ, van Krieken JH, Wobbes T, van Muijen GN (2002) Limitations of cytokeratin 20 RT-PCR to detect disseminated tumour cells in blood and bone marrow with colorectal cancer: expression in controls and downregulation in tumour tissue. Mol Pathol 55:156–163CrossRefPubMed

Welsh JB, Sapinoso LM, Su AI, Kern SG, Wang-Rodriguez J, Moskaluk CA, Frierson HF Jr, Hampton GM (2001) Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 61:5974–5978PubMed

Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792PubMed

Wildi S, Kleeff J, Maruyama H, Maurer CA, Friess H, Buchler MW, Lander AD, Korc M (1999) Characterization of cytokeratin 20 expression in pancreatic and colorectal cancer. Clin Cancer Res 5:2840–2847PubMed

Xiong M, Li W, Zhao J, Jin L, Boerwinkle E (2001) Feature (gene) selection in gene expression-based tumor classification. Mol Genet Metab 73:239–247CrossRefPubMed

Title: Classification of Dukes' B and C colorectal cancers using expression arrays
Authors: Casper Møller Frederiksen
Steen Knudsen
Søren Laurberg
Torben F. Ørntoft
Publication date: 01-05-2003
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 5/2003
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-003-0434-x

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Purpose

Methods

Results

Conclusion

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