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Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-β1 (TGF-β1) acts both as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels of TGF-β1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy and clinical outcome.

Materials and methods

One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field treatment 5 × 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent assay for total TGF-β1 and active TGF-β1. Patients were then followed for 3 years.

Results

Total and active TGF-β1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-β1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-β1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-β1 in plasma were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-β1 in the rectal mucosa (p = 0.038).

Conclusions

Higher levels of total TGF-β1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active TGF-β1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-β1 in rectal mucosa may influence risk of local recurrence. Measurement of TGF-β1 in rectal cancer patients may be of clinical use in the future.

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Acknowledgements

The authors would like to thank Mats Gunnarsson for statistical advice and Kristina Ticehurst for valuable comments and discussions.

Funding

Halland’s Research Council, Gothenburg Medical Society, Swedish Research Council, JK-fonden, Gothenburg, Assar Gabrielsson foundation.

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Authors and Affiliations

  1. Department of Surgery, Sahlgrenska University Hospital/Östra, Göteborg University, 41685, Gothenburg, Sweden

    Eva Angenete, Ingrid Palmgren, Peter Falk & Tom Öresland

  2. Department of Vascular Surgery, Sahlgrenska University Hospital/Sahlgrenska, Göteborg University, Gothenburg, Sweden

    Marcus Langenskiöld

  3. Department of Surgery, Kungsbacka Hospital, Göteborg University, Kungsbacka, Sweden

    Marie-Louise Ivarsson

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  1. Eva Angenete
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  2. Marcus Langenskiöld
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  6. Marie-Louise Ivarsson
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Correspondence to Eva Angenete.

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Angenete, E., Langenskiöld, M., Palmgren, I. et al. Transforming growth factor beta-1 in rectal tumour, mucosa and plasma in relation to radiotherapy and clinical outcome in rectal cancer patients. Int J Colorectal Dis 22, 1331–1338 (2007). https://doi.org/10.1007/s00384-007-0342-7

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