Assessment of alterations in gene expression in recurrent malignant gliomaafter radiotherapy using complementary deoxyribonucleic acid microarrays

OBJECTIVE: We used complementary deoxyribonucleic acid expression microarra ys to assess the effects of radiotherapy on gene expression in glioblastoma multiforme. We hypothesized that postradiation recurrent tumors may demons trate alterations in gene expression from the primary tumor specimen. METHODS: Patients were diagnosed with glioblastoma multiforme at resection of the initial tumor, and they received 60 Gy of fractionated radiotherapy before recurrence. Ribonucleic acid samples from both the primary and the p ostradiation recurrent tumor in each patient were screened and compared usi ng complementary deoxyribonucleic acid expression arrays and Northern blot analysis. RESULTS: Messenger ribonucleic acid levels of growth factors participating in paracrine loops, such as vascular endothelial growth factor and platelet -derived growth factor receptor beta, were decreased in postradiation recur rent tumors as compared with primary tumors in three of four patients. Howe ver, messenger ribonucleic acid levels of growth factors involved in autocr ine loops, such as epidermal growth factor receptor, platelet-derived growt h factor a: platelet-derived growth factor A, and basic fibroblast growth f actor, were decreased in two of four, two of four, three of four, and three of four patients' recurrent tumors, respectively. Microvessel counts demon strated that blood vessel growth was decreased significantly in postradiati on recurrent tumor specimens. CONCLUSION: After radiotherapy of glioblastoma multiforme, levels of paracr ine-acting growth factors are diminished in correspondence with the reducti on in vascular density. In contrast, growth factors that participate in aut ocrine loops demonstrate elevated levels of gene expression. These results suggest that maintenance of autocrine loops may be important in tumor regro wth after radiotherapy.