Late changes in cutaneous gene expression patterns after adjuvant treatment of oral squamous cell carcinoma (OSCC) by radiation therapy.
OBJECTIVE
The objective of this study was to investigate radiation-induced late changes in cutaneous gene expression using a microarray platform and quantitative, real-time, reverse-transcriptase polymerase chain reaction (RT-PCR) validation.


METHODS
Paired irradiated and nonirradiated skin biopsies were obtained from 19 patients with a history of oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant radiotherapy at the time of secondary corrective surgery. Topic-defined PIQOR (Parallel Identification and Quantification of RNAs) skin microarrays were used to compare gene expression profiles between control and irradiated skin sample in 8 patients. The data were validated for matrixmetalloproteinase (MMP)-1 and tissue-inhibitor of matrixmetalloproteinase (TIMP)-1 by RT-PCR for all patients.


RESULTS
Irradiation markedly enhanced the expression of molecules associated with the transforming growth factor (TGF)-beta(1) signaling pathway, blood vessel development, as well as extracellular matrix constitution and turn-over.


CONCLUSIONS
Our data suggest that radiation-induced late changes in cutaneous gene expression mainly affect molecules related to extracellular matrix (ECM)-constitution and-remodeling.
Mueller
Cornelia K
CK
Department of Oral and Maxillofacial Surgery/Plastic Surgery, University of Jena, Germany. cornelia.mueller1@med.uni-jena.de
Thorwarth
Michael
M
Schultze-Mosgau
Stefan
S
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016025:Bone Transplantation / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery; D005109:Extracellular Matrix / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008297:Male; D008339:Mandibular Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000528:radiation effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000528:radiation effects; D020411:Oligonucleotide Array Sequence Analysis; D011832:Radiation Injuries / Q000235:genetics; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated; D019651:Plastic Surgery Procedures; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D016038:Skin Transplantation / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000528:radiation effects; D014945:Wound Healing / Q000528:radiation effects
D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1