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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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.
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).
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.
KeywordsRectal cancer Irradiation TGF-beta Extracellular matrix Distant metastases
The authors would like to thank Mats Gunnarsson for statistical advice and Kristina Ticehurst for valuable comments and discussions.
Halland’s Research Council, Gothenburg Medical Society, Swedish Research Council, JK-fonden, Gothenburg, Assar Gabrielsson foundation.
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