Abstract
BackgroundChemotherapy resistance is reported to correlate with up-regulation of anti-tumor agent transporter ABCB1 (p-gp) in epithelial ovarian cancer (EOC), but the results remain controversial. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association between high ABCB1 status or ABCB1 gene variants and overall survival (OS), progression free survival (PFS), and total response rate (TR) in patients with EOC.Materials and MethodsElectronic searches were performed using Pubmed, EMBASE, Web of Science and Chinese Wanfang databases from January 1990 to February 2016. Summary hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (CIs) were combined using fixed or random-effects models as appropriate.ResultsThirty-eight retrospective studies of 8607 cases qualified for meta-analysis were identified. Our results suggested that ABCB1 over-expression was significantly associated with unfavorable OS (HR = 1.54; 95% CI, 1.25–1.90), PFS (HR = 1.49; 95% CI, 1.22–1.82) and TR (RR = 0.63; 95% CI, 0.54–0.75). After adjustment for age, clinical stage, residual disease, histological type and tumor grade, high ABCB1 status remained to be a significant risk factor for adverse OS and PFS. Patients with recurrent ABCB1 positivity suffered from poorer OS than those with primary ABCB1 positivity. However, stratified by chemotherapy regimen, inverse correlation between high ABCB1 status and poor OS, PFS and TR were only found in patients underwent platinum-based chemotherapy but not in patients received standard platinum/paclitaxel-based chemotherapy. No evidence was found for any association between ABCB1 gene polymorphisms and OS, PFS or TR.ConclusionHigh ABCB1 status is significantly associated with chemo-resistance and poor prognosis in patients with EOC. Large-scale, prospective studies are needed to assess the clinical value of ABCB1 expression in EOC more accurately.
Highlights
Ovarian cancer is the most lethal gynecological malignancy worldwide [1]
Our results suggested that ABCB1 over-expression was significantly associated with unfavorable overall survival (OS) (HR = 1.54; 95% confidence intervals (CIs), 1.25–1.90), progression free survival (PFS) (HR = 1.49; 95% CI, 1.22–1.82) and total response rate (TR) (RR = 0.63; 95% CI, 0.54–0.75)
Stratified by chemotherapy regimen, inverse correlation between high ABCB1 status and poor OS, PFS and TR were only found in patients underwent platinum-based chemotherapy but not in patients received standard platinum/paclitaxel-based chemotherapy
Summary
Ovarian cancer is the most lethal gynecological malignancy worldwide [1]. Epithelial ovarian cancer (EOC) accounts for over 90% of all ovarian cancers [2]. Six cycles of taxane plus platinum chemotherapy represents the most widely used regimen for EOC; other platinum-based regimens included PAC (platinum + doxorubicin + cyclophosphamide) and PC (platinum + cyclophosphamide). This treatment procedure can achieve an overall response rate higher than 70% in patients with ovarian cancer, a great proportion (approximately 75%) of them suffer a recurrence within 2 to 3 years after initial treatment, which leads to poor outcomes [4]. Chemotherapy resistance is reported to correlate with up-regulation of anti-tumor agent transporter ABCB1 (p-gp) in epithelial ovarian cancer (EOC), but the results remain controversial. A systematic review followed by meta-analysis was performed to assess the association between high ABCB1 status or ABCB1 gene variants and overall survival (OS), progression free survival (PFS), and total response rate (TR) in patients with EOC
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