Assessment of alterations in gene expression in recurrent malignant glioma after radiotherapy using complementary deoxyribonucleic acid microarrays.
OBJECTIVE
We used complementary deoxyribonucleic acid expression microarrays to assess the effects of radiotherapy on gene expression in glioblastoma multiforme. We hypothesized that postradiation recurrent tumors may demonstrate 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 postradiation recurrent tumor in each patient were screened and compared using 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 recurrent tumors as compared with primary tumors in three of four patients. However, messenger ribonucleic acid levels of growth factors involved in autocrine loops, such as epidermal growth factor receptor, platelet-derived growth factor alpha, platelet-derived growth factor A, and basic fibroblast growth factor, were decreased in two of four, two of four, three of four, and three of four patients' recurrent tumors, respectively. Microvessel counts demonstrated that blood vessel growth was decreased significantly in postradiation recurrent tumor specimens.


CONCLUSIONS
After radiotherapy of glioblastoma multiforme, levels of paracrine-acting growth factors are diminished in correspondence with the reduction in vascular density. In contrast, growth factors that participate in autocrine loops demonstrate elevated levels of gene expression. These results suggest that maintenance of autocrine loops may be important in tumor regrowth after radiotherapy.
Joki
T
T
Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Carroll
R S
RS
Dunn
I F
IF
Zhang
J
J
Abe
T
T
Black
P M
PM
D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000532:radiotherapy*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis
D018076:DNA, Complementary