Figure 6: Expression and prognostic value of BRCA1 and RRM2 in malignant gliomas.

(a) IHC staining of BRCA1 in normal brain (NB), WHO gr. II, III, IV glioma. Shown are representative sections. Scale bar 50 μm. (b) Quantification of (a) BRCA1 staining. Statistical significance was calculated by one-way ANOVA and Tukey’s multiple comparisons test. (c) A survival curve for BRCA1 negative (n=32); BRCA1 low (< 14.5% of BRCA1⁺ cells, n=35) or BRCA1 high (>14.5% of BRCA1⁺ cells, n=78; median survival of 230 days) glioma patients; Log-rank P value=0.00. Median survival for BRCA1 negative and low patient is not available as >50% of patients were alive at the end of study. (d) A survival curve for BRCA1 high (>14.5% of BRCA1⁺ cells, n=60, median survival of 159 days) and BRCA1 low (<14.5% of BRCA1⁺ cells, n=15; median survival of 251 days) GBM patients. Log-rank P-value=0.293. (e) Quantification of RRM2 staining (% of positive cells). Statistical significance was calculated by one-way ANOVA and Tukey’s multiple comparisons test. (f) A survival curve for RRM2 negative (n=64) and RRM2 positive (n=81; median survival of 222 days) glioma patients, where the median RRM2-positivity is 1% and Log-rank P value=0.00. Median survival for RRM2 negative patients is not available as more than 50% of patients were alive at the end of study. (g) A survival curve for RRM2 positive (n=56, median survival of 148 days) and RRM2 negative (n=19; median survival of 320 days) GBM patients. Log-rank P value=0.23. (h) Spearman correlation test confirmed a positive correlation between the percentage of BRCA1 and RRM2-positive cells in human gliomas (our study dataset). (i) Spearman correlation test confirmed a positive correlation between BRCA1 and RRM2 mRNA expression in human gliomas (REMBRANDT dataset). (*P<0.05, ^**P<0.005, ^***P<0.005, ^****P<0.0001; NS represents non-significance).