A proteomic analysis of the effect of radiation therapy on wound healing in women reconstructed with the TRAM flap

The incidence of breast cancer is still increasing, and with improved cancer treatment, more women live longer with the side effects of their treatment. The response of normal tissue to radiation continues for years after the treatment is completed. The influence of radiotherapy on the outcome of breast reconstructtive surgery remains unpredictable. The combination of two surgical sites of which one is previously irradiated, is rarely encountered in humans and thus compiles a unique opportunity to study the implications of irradiation followed by surgery. The aim of this study was to examine the long-term effect of radiation therapy on the proteins expressed in the wound tissue after a breast reconstruction. Ten patients were included in the study, all treated with radiotherapy after a mastectomy and breast reconstruction with a contralateral pedicled TRAM flap. Expanded poly-tetrafluoretylene polymer tubes were implanted for 10 days, subcutaneously, below the inframammary fold and below the donor site. The protein from the newly synthesized granulation tissue in the tubes was extracted and analyzed for differences in protein expression with 2D gel electrophoresis and mass spectrometry. A total of 676 proteins were detected; of these, 4 proteins changed significantly and were successfully identified. TPM4 and APOA4 from the radiation treated tissue were shown to be significantly decreased, whereas IGKC and VDAC1 were found to be significantly increased. The proteomic technique combined with the ePTFE tube wound model can elucidate some of the molecular alterations in the wound healing induced by radiation therapy. The protein modifications of TPM4, APOA4, IGKC and VDAC1 may influence the cell proliferation, apoptosis and the inflammation of the tissue repair process.