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Rad51 protein expression and survival in patients with glioblastoma multiforme
James W Welsh1, Ron K Ellsworth, Rachit Kumar
1Department of Radiation Oncology, University of Arizona College of Medicine, Tucson, AZ, USA.
Purpose:
Treatment of glioblastoma multiforme (GBM) continues to pose a significant therapeutic challenge, with most tumors recurring within the previously irradiated tumor bed. To improve outcomes, we must be able to identify and treat resistant cell populations. Rad51, an enzyme involved in homologous recombinational repair, leads to increased resistance of tumor cells to cytotoxic treatments such as radiotherapy. We hypothesized that Rad51 might contribute to GBM's apparent radioresistance and consequently influence survival.
Methods And Materials:
A total of 68 patients with an initial diagnosis of GBM were retrospectively evaluated; for 10 of these patients, recurrent tumor specimens were used to construct a tissue microarray. Rad51 protein expression was then correlated with the actual and predicted survival using recursive partitioning analysis.
Results:
Rad51 protein was elevated in 53% of the GBM specimens at surgery. The Rad51 levels correlated directly with survival, with a median survival of 15 months for patients with elevated Rad51 compared with 9 months for patients with low or absent levels of Rad51 (p = .05). At disease recurrence, 70% of patients had additional increases in Rad51 protein. Increased Rad51 levels at disease recurrence similarly predicted for improved overall survival, with a mean survival of 16 months from the second craniotomy compared with only 4 months for patients with low Rad51 levels (p = .13).
Conclusion:
Elevated levels of the double-stranded DNA repair protein Rad51 predicted for an increase survival duration in patients with GBM, at both initial tumor presentation and disease recurrence.
Insights
Elevated Rad51 protein levels in glioblastoma multiforme (GBM) correlate with longer survival. This DNA repair enzyme
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) treatment faces challenges due to tumor recurrence.
- Identifying radioresistant cell populations is crucial for improving GBM patient outcomes.
- Rad51, a homologous recombinational repair enzyme, is implicated in tumor cell resistance to cytotoxic treatments like radiotherapy.
Purpose of the Study:
- To investigate the role of Rad51 in glioblastoma multiforme (GBM) radioresistance.
- To determine if Rad51 expression levels correlate with patient survival in GBM.
- To assess changes in Rad51 expression at disease recurrence.
Main Methods:
- Retrospective analysis of 68 GBM patients.
- Construction of tissue microarrays from initial and recurrent tumor specimens.
- Correlation of Rad51 protein expression with patient survival using recursive partitioning analysis.
Main Results:
- Rad51 protein was elevated in 53% of initial GBM specimens.
- Elevated Rad51 correlated with longer median survival (15 months vs. 9 months).
- Rad51 levels increased at recurrence in 70% of patients, predicting improved survival post-recurrence.
Conclusions:
- Elevated Rad51 protein levels at initial presentation predict longer survival in GBM patients.
- Increased Rad51 expression at disease recurrence also indicates a better prognosis.
- Rad51 may serve as a predictive biomarker for GBM treatment response and survival.
