TITLE:
A proteomic analysis of the effect of radiation therapy on wound healing in women reconstructed with the TRAM flap
AUTHORS:
Bekka O. Christensen, Jens Overgaard, Henrik Vorum, Bent Honore, Tine E. Damsgaard
KEYWORDS:
TRAM Flap; Radiation Therapy; Reconstructive Surgery; Human; Proteomics; TPM; VDAC; APOA4
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.11,
November
28,
2013
ABSTRACT:
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.