Late changes in cutaneous gene expression patterns after adjuvant treatment of oral squamous cell carcinoma (OSCC) by radiation therapy

ObjectiveThe 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.Study designPaired 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.ResultsIrradiation markedly enhanced the expression of molecules associated with the transforming growth factor (TGF)-β1 signaling pathway, blood vessel development, as well as extracellular matrix constitution and turn-over.ConclusionsOur data suggest that radiation-induced late changes in cutaneous gene expression mainly affect molecules related to extracellular matrix (ECM)-constitution and-remodeling.