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Radiation induces different changes in expression profiles of normal rectal tissue compared with rectal carcinoma.
- Source :
-
Virchows Archiv : an international journal of pathology [Virchows Arch] 2005 Feb; Vol. 446 (2), pp. 127-35. Date of Electronic Publication: 2004 Dec 16. - Publication Year :
- 2005
-
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.<br />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.<br />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.<br />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).
- Subjects :
- Apoptosis genetics
Cell Adhesion Molecules genetics
Cytokines genetics
Gene Expression Regulation, Neoplastic radiation effects
Genes, Tumor Suppressor
Humans
Immunohistochemistry
Interleukin-8 genetics
Ki-67 Antigen genetics
Metalloproteases genetics
Oligonucleotide Array Sequence Analysis
Preoperative Care
Prospective Studies
Radiotherapy, Adjuvant
Rectal Neoplasms surgery
Rectum chemistry
Serpins genetics
Gene Expression radiation effects
Rectal Neoplasms genetics
Rectal Neoplasms radiotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 0945-6317
- Volume :
- 446
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Virchows Archiv : an international journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 15602683
- Full Text :
- https://doi.org/10.1007/s00428-004-1160-8