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Radiation induces different changes in expression profiles of normal rectal tissue compared with rectal carcinoma

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Abstract

Purpose

Radiotherapy is a very effective adjuvant treatment for rectal cancer with little side effects. Its killing effect on tumor cells seems to be more profound than the effect on normal tissue. The molecular events caused by irradiation are mainly analyzed in in vitro and animal models; investigations on human material are rare. In the current study, we analyzed the effects of irradiation on gene expression in normal and tumor tissue of rectal cancer patients.

Methods and materials

Normal and carcinoma tissue of patients from a randomized clinical trial of the benefits of preoperative radiotherapy were analyzed using the Affymetrix Human Cancer Gene Chip. Preoperative radiotherapy was given within 5 days prior to surgery. Results for normal tissue and tumor were compared to investigate the radiation-related differences between normal and tumor cells. We clustered the differentially expressed genes based on their functional annotation. Results were compared with immunohistochemical and literature data.

Results

The majority of the investigated cancer-related genes remained unchanged by irradiation (92% in tumor tissue and 93% in normal tissue). The differentially expressed genes varied between tumor and normal tissue except for maspin and IL-8. Both in tumor and normal tissue, differentially expressed genes were present related to cell signaling and cycle control, apoptosis and cell survival and tissue response and repair. However, the spectrum of affected genes was totally different.

Conclusion

Pre-existing differences in gene expression between normal tissue and tumor tissue might explain the differences in their responses to radiation. This change in response may explain the clinical beneficial effect of radiotherapy on tumor cells (low local recurrence rate) and the less severe effects on normal tissue (minor side effects).

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Acknowledgement

Grant support was provided by National Health Council (Ontwikkelingsgeneeskunde OWG 97/026).

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Authors and Affiliations

  1. Departments of Pathology, Leiden University Medical Center, Leiden, The Netherlands

    I. D. Nagtegaal

  2. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    I. D. Nagtegaal, E. Kapiteijn & C. J. H. van de Velde

  3. Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

    C. G. S. Gaspar & R. Fodde

  4. Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands

    L. T. C. Peltenburg & C. A. M. Marijnen

  5. Department of Pathology, University Medical Center St. Radboud, PO Box 9101, 6500 HB , Nijmegen, The Netherlands

    I. D. Nagtegaal & J. H. J. M. van Krieken

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  1. I. D. Nagtegaal
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  2. C. G. S. Gaspar
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  3. L. T. C. Peltenburg
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Correspondence to I. D. Nagtegaal.

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Nagtegaal, I.D., Gaspar, C.G.S., Peltenburg, L.T.C. et al. Radiation induces different changes in expression profiles of normal rectal tissue compared with rectal carcinoma. Virchows Arch 446, 127–135 (2005). https://doi.org/10.1007/s00428-004-1160-8

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  • DOI: https://doi.org/10.1007/s00428-004-1160-8

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