Skip to main content

Advertisement

SpringerLink
Log in

Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Colorectal cancer is one of the leading causes of cancer deaths in the Western world. A better understanding of the development and progression of colorectal carcinoma is needed to define novel targets and strategies for treatment.

Patients/methods

Gene expression profiles were determined for primary tumors of 10 locally restricted (T3N0M0), 8 lymphatically metastasized (T3N+M0), 7 systemically metastasized (T3N+M1) colorectal carcinomas, and 6 specimens of normal colorectal tissue by histology-guided oligonucleotide microarray analysis.

Results

A total of 1,995 genes were differently regulated in primary tumors of colorectal carcinoma compared with normal colorectal tissue. Besides common features of dedifferentiation and different expression of genes involved in cell division, cell adhesion, angiogenesis, signal transduction and metabolism we observed a deregulation of genes with an as yet unclear function. We identified 126 genes that were subsequently up- and 204 genes down-regulated during tumor progression. Furthermore, we found a cluster of five genes exclusively up-regulated in primary tumors of systemically metastasized colorectal carcinomas. A comparison of locally restricted (T3N0M0) and systemically metastasized (T3N+M1) primary tumors showed 50 deregulated genes with a massive down-regulation of immune-modulatory genes in primary tumors of systemically metastasized carcinomas. Primary tumors of lymphatically (T3N+M0) and systemically metastasized (T3N+M1) carcinomas differed in the expression of 19 genes.

Conclusion

These results provide an additional step toward the identification of crucial genes for the progression of colorectal cancer and the identification of novel treatment targets or strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Pohl C, Hombach A, Kruis W (2000) Chronic inflammatory bowel disease and cancer. Hepatogastroenterology 47:57–70

    CAS  PubMed  Google Scholar 

  2. Muto T, Bussey HJ, Morson BC (1975) The evolution of cancer of the colon and rectum. Cancer 36:2251–2270

    CAS  PubMed  Google Scholar 

  3. Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M (1987) Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327:298–303

    Article  CAS  PubMed  Google Scholar 

  4. Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, van Tuinen P, Ledbetter DH, Barker DF, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221

    CAS  PubMed  Google Scholar 

  5. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P (1991) Mutation of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–669

    CAS  PubMed  Google Scholar 

  6. Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819

    CAS  PubMed  Google Scholar 

  7. 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 61:3124–3130

    CAS  PubMed  Google Scholar 

  8. Lin Y, Furukawa Y, Tsunoda T, Yue C, Yang K, Nakamura Y (2002) Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas. Oncogene 21:4120–4128

    Article  CAS  PubMed  Google Scholar 

  9. 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 96:6745–6750

    Article  CAS  PubMed  Google Scholar 

  10. 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 62:4352–4363

    CAS  PubMed  Google Scholar 

  11. Kwon HC, Kim SH, Roh MS, Kim JS, Lee HS, Choi HJ, Jeong JS, Kim HJ, Hwang TH (2004) Gene expression profiling in lymph node-positive and lymph node-negative colorectal cancer. Dis Colon Rectum 47:141–152

    Article  PubMed  Google Scholar 

  12. Frederiksen CM, Knudsen S, Laurberg S, Orntoft TF (2003) Classification of Dukes B and C colorectal cancers using expression arrays. J Cancer Res Clin Oncol 129:263–271

    PubMed  Google Scholar 

  13. Matrisian LM, Cunha GR, Mohla S (2001) Epithelial-stromal interactions and tumor progression: meeting summary and future directions. Cancer Res 61:3844–3846

    CAS  PubMed  Google Scholar 

  14. Martin-Lluesma S, Stucke VM, Nigg EA (2002) Role of Hec1 in spindle checkpoint signalling and kinetochore recruitment of MAD1/MAD2. Science 297:2267–2270

    Article  CAS  PubMed  Google Scholar 

  15. Wang X, Jin DJ, Ng RW, Feng H, Wong YC, Cheung AL, Tsao SW (2002) Significance of MAD2 expression to mitotic checkpoint control of ovarian cancer cells. Cancer Res 62:1662–1668

    CAS  PubMed  Google Scholar 

  16. Behrens P, Brinkmann U, Wellmann A (2003) CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis 8:39–44

    Article  CAS  PubMed  Google Scholar 

  17. O’Connell MJ, Krien MJ, Hunter T (2003) Never say never. The NIMA-related protein kinases in mitotic control. Trends Cell Biol 13:221–228

    Article  CAS  PubMed  Google Scholar 

  18. Liu ST, Hittle JC, Jablonski SA, Campbell MS, Yoda K, Yen TJ (2003) Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis. Nat Cell Biol 5:341–345

    Article  CAS  PubMed  Google Scholar 

  19. Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, Romans KE, Chot MA, Lengauer C, Kinzler KW, Vogelstein B (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294:1343–1346

    Article  CAS  PubMed  Google Scholar 

  20. Agrawal D, Chen T, Irby R, Quackenbush J, Chanbers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ (2002) Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94:513–521

    CAS  PubMed  Google Scholar 

  21. Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509–514

    Article  CAS  PubMed  Google Scholar 

  22. Bourguignon LY, Zhu H, Shao L, Zhu D, Chen YW (1999) Rho-kinase (ROK) promotes CD44v(3,8–10)-ankyrin interaction and tumor cell migration in metastatic breast cancer cells. Cell Motil Cytoskeleton 43:269–287

    Article  CAS  PubMed  Google Scholar 

  23. Fritz G, Just I, Kaina B (1999) Rho GTPases are over-expressed in human tumors. Int J Cancer 81:682–687

    Article  CAS  PubMed  Google Scholar 

  24. Fukuda T, Kido A, Kajuno K, Tsutsumi M, Miyauchi Y, Tsujiuchi T, Konishi Y, Hino O (1999) Cloning of differentially expressed genes in highly and low metastatic rat osteosarcomas by a modified cDNA-AFLP method. Biochem Biophys Res Commun 261:35–40

    Article  CAS  PubMed  Google Scholar 

  25. Pardo J, Balkow S, Anel A, Simon MM (2002) Granzymes are essential for natural killer cell-mediated and perf-facilitated tumor control. Eur J Immunol 32:2881–2887

    Article  CAS  PubMed  Google Scholar 

  26. Mulder WM, Bloemena E, Stukart MJ, Kummer JA, Wagstaff J, Scheper RJ (1997) T cell receptor-zeta and granzyme B expression in mononuclear cell infiltrates in normal colon mucosa and colon carcinoma. Gut 40:113–119

    CAS  PubMed  Google Scholar 

  27. Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong J, Fukayama M, Kodama T, Aburatani H (2002) Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Cancer Res 62:233–240

    CAS  PubMed  Google Scholar 

  28. Olschwang S, Hamelin R, Laurent-Puig P, Thuille B, De Rycke Y, Li YJ, Muzeau F, Girodet J, Salmon RJ, Thomas G (1997) Alternative genetic pathways in colorectal carcinogenesis. Proc Natl Acad Sci 94:12122–12127

    Article  CAS  PubMed  Google Scholar 

  29. Ohno S, Tachibana M, Fujii T, Ueda S, Kubota H, Nagasue N (2002) Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma. Int J Cancer 97:770–774

    Article  CAS  PubMed  Google Scholar 

  30. Arias AM (2001) Epithelial mesenchymal interactions in cancer and development. Cell 105:425–431

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Carmen Marthen and Gabriela Jusek for excellent technical assistance.

Author information

Authors and Affiliations

  1. Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany

    Jan Friederichs, Robert Rosenberg, Klaus-Peter Janssen, Christian Maeckl, Hjalmar Nekarda, Bernhard Holzmann & Joerg-Ruediger Siewert

  2. Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Joerg Mages

Authors
  1. Jan Friederichs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Rosenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joerg Mages
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Klaus-Peter Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Maeckl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hjalmar Nekarda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bernhard Holzmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joerg-Ruediger Siewert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Friederichs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friederichs, J., Rosenberg, R., Mages, J. et al. Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression. Int J Colorectal Dis 20, 391–402 (2005). https://doi.org/10.1007/s00384-004-0722-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-004-0722-1

Keywords

Search

Navigation