7% of total) bared high/positive BRCA1. An interesting conclusion was found: opposite to platinum-based
treatment, NSCLC patients bearing high/positive BRCA1 were more likely to respond to toxal-based treatment when compared with those bearing the low/negative (low/negative vs high/positive: 26.0% vs 46.1%, OR = 0.41, 95%CI = 0.27-0.64, I2 = 0.0%, P = 0.61 for heterogeneity) selleck chemicals llc (Figure 5). No publication bias existed (P = 0.84). Table 2 The summary meta-analysis results of association between BRCA1 level with objective response rate (ORR), overall survival (OS) and event-free survival (EFS) in platinum- and toxal-based treatment Comparisons No of studies (patients) Percentage of low/negative BRCA1 (%) ORR: low/negative vs high/postive (%) Overall OR/HR (95% CI) fixed and random Heterogeneity test P for publication bias Platinum-based ORR overall 16(1330) 44.4 48.9 vs 38.1 1.70 (1.32, 2.18), 1.80(1.26,2.55) I 2 = 44.7%,P = 0.03 0.15 Method
IHC 13(1066) 44.5 50.7 vs 39.0 1.54(1.17,2.00), 1.59(1.07,2.36) I 2 = 44.8%,P = 0.03 0.41 RT-PCR 4(264) 44.3 43.7 vs 25 2.91 (1.55, 3.83), 2.91(1.55,5.47) I 2 = 0.0%, P = 0.52 0.76 Origin East-Asian 14(1133) 45.4 51.0 vs 36.0 1.68(1.30,2.19), 1.79(1.24,2.60) I 2 = 39.9%,P = 0.04 0.10 Caucasian 3(197) 38.6 39.8 vs 33.4 1.79 (0.84, 3.83), 1.77(0.50,6.28) I 2 = 63.6%,P = 0.06 0.90 OS 8(733) – - 1.58(1.27,1.97), 1.65(1.19,2.89) I 2 = 48.4%,P = 0.03 0.13 EFS 6(599) – - 1.62(1.28,2.05), 1.60(1.07,2.39) I 2 = 54.5%,P = 0.02 0.88 Toxal-based ORR overall 4(376) GSK1120212 cost 41.3 26.0 vs 46.1 0.41(0.26,0.64), 0.41(0.27,0.64) I 2 = 0.0%, P = 0.61 0.84 Discussion Although the relationship between
BRCA1 expression and chemotherapy outcomes of NSCLC has been investigated by previous studies, the results were inconsistent and some were even conflicting. So a systematic review and meta-analysis based on the published literature was necessary to give further insights on this conflicting issue. Our meta-analysis showed that for platinum-based chemotherapy, low/negative BRCA1 expression were associated with not only better ORR, but also longer OS and EFS, but for toxal-based chemotherapy, high/positive BRCA1 was associated FER with better ORR. Platinum agents can bind to DNA and form complexes thus inducing intra- and inter-strand DNA, as well as DNA-protein cross-links and results in cell growth inhibition and apoptosis. As one of ant-tubulin agents, taxol inhibits cell division by enhancing formation and stabilization of microtubules and disrupts the mitotic spindle assembly, and a surveillance mechanism known as the spindle checkpoint at the metaphase-anaphase transition have been activated.